GH-131798: Split up and optimize CALL_ISINSTANCE (GH-133339)

11 files changed, 392 insertions, 301 deletions

diff --git a/Include/internal/pycore_opcode_metadata.h b/Include/internal/pycore_opcode_metadata.h
index 0e34074f160..e55e26783a6 100644
--- a/Include/internal/pycore_opcode_metadata.h
+++ b/Include/internal/pycore_opcode_metadata.h
@@ -113,7 +113,7 @@ int _PyOpcode_num_popped(int opcode, int oparg)  {
         case CALL_INTRINSIC_2:
             return 2;
         case CALL_ISINSTANCE:
-            return 2 + oparg;
+            return 4;
         case CALL_KW:
             return 3 + oparg;
         case CALL_KW_BOUND_METHOD:
@@ -1115,7 +1115,7 @@ const struct opcode_metadata _PyOpcode_opcode_metadata[267] = {
     [CALL_FUNCTION_EX] = { true, INSTR_FMT_IX, HAS_EVAL_BREAK_FLAG | HAS_ERROR_FLAG | HAS_ERROR_NO_POP_FLAG | HAS_ESCAPES_FLAG },
     [CALL_INTRINSIC_1] = { true, INSTR_FMT_IB, HAS_ARG_FLAG | HAS_ERROR_FLAG | HAS_ESCAPES_FLAG },
     [CALL_INTRINSIC_2] = { true, INSTR_FMT_IB, HAS_ARG_FLAG | HAS_ERROR_FLAG | HAS_ESCAPES_FLAG },
-    [CALL_ISINSTANCE] = { true, INSTR_FMT_IBC00, HAS_ARG_FLAG | HAS_DEOPT_FLAG | HAS_ERROR_FLAG | HAS_ERROR_NO_POP_FLAG | HAS_ESCAPES_FLAG },
+    [CALL_ISINSTANCE] = { true, INSTR_FMT_IXC00, HAS_DEOPT_FLAG | HAS_ERROR_FLAG | HAS_ERROR_NO_POP_FLAG | HAS_ESCAPES_FLAG },
     [CALL_KW] = { true, INSTR_FMT_IBC00, HAS_ARG_FLAG | HAS_ERROR_FLAG | HAS_ERROR_NO_POP_FLAG | HAS_ESCAPES_FLAG },
     [CALL_KW_BOUND_METHOD] = { true, INSTR_FMT_IBC00, HAS_ARG_FLAG | HAS_DEOPT_FLAG | HAS_EXIT_FLAG | HAS_ERROR_FLAG | HAS_ESCAPES_FLAG },
     [CALL_KW_NON_PY] = { true, INSTR_FMT_IBC00, HAS_ARG_FLAG | HAS_EVAL_BREAK_FLAG | HAS_EXIT_FLAG | HAS_ERROR_FLAG | HAS_ESCAPES_FLAG },
@@ -1363,7 +1363,7 @@ _PyOpcode_macro_expansion[256] = {
     [CALL_BUILTIN_O] = { .nuops = 2, .uops = { { _CALL_BUILTIN_O, OPARG_SIMPLE, 3 }, { _CHECK_PERIODIC, OPARG_SIMPLE, 3 } } },
     [CALL_INTRINSIC_1] = { .nuops = 1, .uops = { { _CALL_INTRINSIC_1, OPARG_SIMPLE, 0 } } },
     [CALL_INTRINSIC_2] = { .nuops = 1, .uops = { { _CALL_INTRINSIC_2, OPARG_SIMPLE, 0 } } },
-    [CALL_ISINSTANCE] = { .nuops = 1, .uops = { { _CALL_ISINSTANCE, OPARG_SIMPLE, 3 } } },
+    [CALL_ISINSTANCE] = { .nuops = 3, .uops = { { _GUARD_THIRD_NULL, OPARG_SIMPLE, 3 }, { _GUARD_CALLABLE_ISINSTANCE, OPARG_SIMPLE, 3 }, { _CALL_ISINSTANCE, OPARG_SIMPLE, 3 } } },
     [CALL_KW_BOUND_METHOD] = { .nuops = 6, .uops = { { _CHECK_PEP_523, OPARG_SIMPLE, 1 }, { _CHECK_METHOD_VERSION_KW, 2, 1 }, { _EXPAND_METHOD_KW, OPARG_SIMPLE, 3 }, { _PY_FRAME_KW, OPARG_SIMPLE, 3 }, { _SAVE_RETURN_OFFSET, OPARG_SAVE_RETURN_OFFSET, 3 }, { _PUSH_FRAME, OPARG_SIMPLE, 3 } } },
     [CALL_KW_NON_PY] = { .nuops = 3, .uops = { { _CHECK_IS_NOT_PY_CALLABLE_KW, OPARG_SIMPLE, 3 }, { _CALL_KW_NON_PY, OPARG_SIMPLE, 3 }, { _CHECK_PERIODIC, OPARG_SIMPLE, 3 } } },
     [CALL_KW_PY] = { .nuops = 5, .uops = { { _CHECK_PEP_523, OPARG_SIMPLE, 1 }, { _CHECK_FUNCTION_VERSION_KW, 2, 1 }, { _PY_FRAME_KW, OPARG_SIMPLE, 3 }, { _SAVE_RETURN_OFFSET, OPARG_SAVE_RETURN_OFFSET, 3 }, { _PUSH_FRAME, OPARG_SIMPLE, 3 } } },
diff --git a/Include/internal/pycore_uop_ids.h b/Include/internal/pycore_uop_ids.h
index d3d2b716e2c..71a288a3a39 100644
--- a/Include/internal/pycore_uop_ids.h
+++ b/Include/internal/pycore_uop_ids.h
@@ -43,125 +43,127 @@ extern "C" {
 #define _CALL_BUILTIN_O 323
 #define _CALL_INTRINSIC_1 CALL_INTRINSIC_1
 #define _CALL_INTRINSIC_2 CALL_INTRINSIC_2
-#define _CALL_ISINSTANCE CALL_ISINSTANCE
-#define _CALL_KW_NON_PY 324
-#define _CALL_LEN 325
+#define _CALL_ISINSTANCE 324
+#define _CALL_KW_NON_PY 325
+#define _CALL_LEN 326
 #define _CALL_LIST_APPEND CALL_LIST_APPEND
-#define _CALL_METHOD_DESCRIPTOR_FAST 326
-#define _CALL_METHOD_DESCRIPTOR_FAST_WITH_KEYWORDS 327
-#define _CALL_METHOD_DESCRIPTOR_NOARGS 328
-#define _CALL_METHOD_DESCRIPTOR_O 329
-#define _CALL_NON_PY_GENERAL 330
-#define _CALL_STR_1 331
-#define _CALL_TUPLE_1 332
-#define _CALL_TYPE_1 333
-#define _CHECK_AND_ALLOCATE_OBJECT 334
-#define _CHECK_ATTR_CLASS 335
-#define _CHECK_ATTR_METHOD_LAZY_DICT 336
-#define _CHECK_CALL_BOUND_METHOD_EXACT_ARGS 337
+#define _CALL_METHOD_DESCRIPTOR_FAST 327
+#define _CALL_METHOD_DESCRIPTOR_FAST_WITH_KEYWORDS 328
+#define _CALL_METHOD_DESCRIPTOR_NOARGS 329
+#define _CALL_METHOD_DESCRIPTOR_O 330
+#define _CALL_NON_PY_GENERAL 331
+#define _CALL_STR_1 332
+#define _CALL_TUPLE_1 333
+#define _CALL_TYPE_1 334
+#define _CHECK_AND_ALLOCATE_OBJECT 335
+#define _CHECK_ATTR_CLASS 336
+#define _CHECK_ATTR_METHOD_LAZY_DICT 337
+#define _CHECK_CALL_BOUND_METHOD_EXACT_ARGS 338
 #define _CHECK_EG_MATCH CHECK_EG_MATCH
 #define _CHECK_EXC_MATCH CHECK_EXC_MATCH
-#define _CHECK_FUNCTION 338
-#define _CHECK_FUNCTION_EXACT_ARGS 339
-#define _CHECK_FUNCTION_VERSION 340
-#define _CHECK_FUNCTION_VERSION_INLINE 341
-#define _CHECK_FUNCTION_VERSION_KW 342
-#define _CHECK_IS_NOT_PY_CALLABLE 343
-#define _CHECK_IS_NOT_PY_CALLABLE_KW 344
-#define _CHECK_MANAGED_OBJECT_HAS_VALUES 345
-#define _CHECK_METHOD_VERSION 346
-#define _CHECK_METHOD_VERSION_KW 347
-#define _CHECK_PEP_523 348
-#define _CHECK_PERIODIC 349
-#define _CHECK_PERIODIC_IF_NOT_YIELD_FROM 350
-#define _CHECK_RECURSION_REMAINING 351
-#define _CHECK_STACK_SPACE 352
-#define _CHECK_STACK_SPACE_OPERAND 353
-#define _CHECK_VALIDITY 354
-#define _COMPARE_OP 355
-#define _COMPARE_OP_FLOAT 356
-#define _COMPARE_OP_INT 357
-#define _COMPARE_OP_STR 358
-#define _CONTAINS_OP 359
-#define _CONTAINS_OP_DICT 360
-#define _CONTAINS_OP_SET 361
+#define _CHECK_FUNCTION 339
+#define _CHECK_FUNCTION_EXACT_ARGS 340
+#define _CHECK_FUNCTION_VERSION 341
+#define _CHECK_FUNCTION_VERSION_INLINE 342
+#define _CHECK_FUNCTION_VERSION_KW 343
+#define _CHECK_IS_NOT_PY_CALLABLE 344
+#define _CHECK_IS_NOT_PY_CALLABLE_KW 345
+#define _CHECK_MANAGED_OBJECT_HAS_VALUES 346
+#define _CHECK_METHOD_VERSION 347
+#define _CHECK_METHOD_VERSION_KW 348
+#define _CHECK_PEP_523 349
+#define _CHECK_PERIODIC 350
+#define _CHECK_PERIODIC_IF_NOT_YIELD_FROM 351
+#define _CHECK_RECURSION_REMAINING 352
+#define _CHECK_STACK_SPACE 353
+#define _CHECK_STACK_SPACE_OPERAND 354
+#define _CHECK_VALIDITY 355
+#define _COMPARE_OP 356
+#define _COMPARE_OP_FLOAT 357
+#define _COMPARE_OP_INT 358
+#define _COMPARE_OP_STR 359
+#define _CONTAINS_OP 360
+#define _CONTAINS_OP_DICT 361
+#define _CONTAINS_OP_SET 362
 #define _CONVERT_VALUE CONVERT_VALUE
 #define _COPY COPY
 #define _COPY_FREE_VARS COPY_FREE_VARS
-#define _CREATE_INIT_FRAME 362
+#define _CREATE_INIT_FRAME 363
 #define _DELETE_ATTR DELETE_ATTR
 #define _DELETE_DEREF DELETE_DEREF
 #define _DELETE_FAST DELETE_FAST
 #define _DELETE_GLOBAL DELETE_GLOBAL
 #define _DELETE_NAME DELETE_NAME
 #define _DELETE_SUBSCR DELETE_SUBSCR
-#define _DEOPT 363
+#define _DEOPT 364
 #define _DICT_MERGE DICT_MERGE
 #define _DICT_UPDATE DICT_UPDATE
-#define _DO_CALL 364
-#define _DO_CALL_FUNCTION_EX 365
-#define _DO_CALL_KW 366
+#define _DO_CALL 365
+#define _DO_CALL_FUNCTION_EX 366
+#define _DO_CALL_KW 367
 #define _END_FOR END_FOR
 #define _END_SEND END_SEND
-#define _ERROR_POP_N 367
+#define _ERROR_POP_N 368
 #define _EXIT_INIT_CHECK EXIT_INIT_CHECK
-#define _EXPAND_METHOD 368
-#define _EXPAND_METHOD_KW 369
-#define _FATAL_ERROR 370
+#define _EXPAND_METHOD 369
+#define _EXPAND_METHOD_KW 370
+#define _FATAL_ERROR 371
 #define _FORMAT_SIMPLE FORMAT_SIMPLE
 #define _FORMAT_WITH_SPEC FORMAT_WITH_SPEC
-#define _FOR_ITER 371
-#define _FOR_ITER_GEN_FRAME 372
-#define _FOR_ITER_TIER_TWO 373
+#define _FOR_ITER 372
+#define _FOR_ITER_GEN_FRAME 373
+#define _FOR_ITER_TIER_TWO 374
 #define _GET_AITER GET_AITER
 #define _GET_ANEXT GET_ANEXT
 #define _GET_AWAITABLE GET_AWAITABLE
 #define _GET_ITER GET_ITER
 #define _GET_LEN GET_LEN
 #define _GET_YIELD_FROM_ITER GET_YIELD_FROM_ITER
-#define _GUARD_BINARY_OP_EXTEND 374
-#define _GUARD_CALLABLE_LEN 375
-#define _GUARD_CALLABLE_STR_1 376
-#define _GUARD_CALLABLE_TUPLE_1 377
-#define _GUARD_CALLABLE_TYPE_1 378
-#define _GUARD_DORV_NO_DICT 379
-#define _GUARD_DORV_VALUES_INST_ATTR_FROM_DICT 380
-#define _GUARD_GLOBALS_VERSION 381
-#define _GUARD_IS_FALSE_POP 382
-#define _GUARD_IS_NONE_POP 383
-#define _GUARD_IS_NOT_NONE_POP 384
-#define _GUARD_IS_TRUE_POP 385
-#define _GUARD_KEYS_VERSION 386
-#define _GUARD_NOS_DICT 387
-#define _GUARD_NOS_FLOAT 388
-#define _GUARD_NOS_INT 389
-#define _GUARD_NOS_LIST 390
-#define _GUARD_NOS_NULL 391
-#define _GUARD_NOS_TUPLE 392
-#define _GUARD_NOS_UNICODE 393
-#define _GUARD_NOT_EXHAUSTED_LIST 394
-#define _GUARD_NOT_EXHAUSTED_RANGE 395
-#define _GUARD_NOT_EXHAUSTED_TUPLE 396
-#define _GUARD_TOS_ANY_SET 397
-#define _GUARD_TOS_DICT 398
-#define _GUARD_TOS_FLOAT 399
-#define _GUARD_TOS_INT 400
-#define _GUARD_TOS_LIST 401
-#define _GUARD_TOS_SLICE 402
-#define _GUARD_TOS_TUPLE 403
-#define _GUARD_TOS_UNICODE 404
-#define _GUARD_TYPE_VERSION 405
-#define _GUARD_TYPE_VERSION_AND_LOCK 406
+#define _GUARD_BINARY_OP_EXTEND 375
+#define _GUARD_CALLABLE_ISINSTANCE 376
+#define _GUARD_CALLABLE_LEN 377
+#define _GUARD_CALLABLE_STR_1 378
+#define _GUARD_CALLABLE_TUPLE_1 379
+#define _GUARD_CALLABLE_TYPE_1 380
+#define _GUARD_DORV_NO_DICT 381
+#define _GUARD_DORV_VALUES_INST_ATTR_FROM_DICT 382
+#define _GUARD_GLOBALS_VERSION 383
+#define _GUARD_IS_FALSE_POP 384
+#define _GUARD_IS_NONE_POP 385
+#define _GUARD_IS_NOT_NONE_POP 386
+#define _GUARD_IS_TRUE_POP 387
+#define _GUARD_KEYS_VERSION 388
+#define _GUARD_NOS_DICT 389
+#define _GUARD_NOS_FLOAT 390
+#define _GUARD_NOS_INT 391
+#define _GUARD_NOS_LIST 392
+#define _GUARD_NOS_NULL 393
+#define _GUARD_NOS_TUPLE 394
+#define _GUARD_NOS_UNICODE 395
+#define _GUARD_NOT_EXHAUSTED_LIST 396
+#define _GUARD_NOT_EXHAUSTED_RANGE 397
+#define _GUARD_NOT_EXHAUSTED_TUPLE 398
+#define _GUARD_THIRD_NULL 399
+#define _GUARD_TOS_ANY_SET 400
+#define _GUARD_TOS_DICT 401
+#define _GUARD_TOS_FLOAT 402
+#define _GUARD_TOS_INT 403
+#define _GUARD_TOS_LIST 404
+#define _GUARD_TOS_SLICE 405
+#define _GUARD_TOS_TUPLE 406
+#define _GUARD_TOS_UNICODE 407
+#define _GUARD_TYPE_VERSION 408
+#define _GUARD_TYPE_VERSION_AND_LOCK 409
 #define _IMPORT_FROM IMPORT_FROM
 #define _IMPORT_NAME IMPORT_NAME
-#define _INIT_CALL_BOUND_METHOD_EXACT_ARGS 407
-#define _INIT_CALL_PY_EXACT_ARGS 408
-#define _INIT_CALL_PY_EXACT_ARGS_0 409
-#define _INIT_CALL_PY_EXACT_ARGS_1 410
-#define _INIT_CALL_PY_EXACT_ARGS_2 411
-#define _INIT_CALL_PY_EXACT_ARGS_3 412
-#define _INIT_CALL_PY_EXACT_ARGS_4 413
-#define _INSERT_NULL 414
+#define _INIT_CALL_BOUND_METHOD_EXACT_ARGS 410
+#define _INIT_CALL_PY_EXACT_ARGS 411
+#define _INIT_CALL_PY_EXACT_ARGS_0 412
+#define _INIT_CALL_PY_EXACT_ARGS_1 413
+#define _INIT_CALL_PY_EXACT_ARGS_2 414
+#define _INIT_CALL_PY_EXACT_ARGS_3 415
+#define _INIT_CALL_PY_EXACT_ARGS_4 416
+#define _INSERT_NULL 417
 #define _INSTRUMENTED_FOR_ITER INSTRUMENTED_FOR_ITER
 #define _INSTRUMENTED_INSTRUCTION INSTRUMENTED_INSTRUCTION
 #define _INSTRUMENTED_JUMP_FORWARD INSTRUMENTED_JUMP_FORWARD
@@ -171,163 +173,163 @@ extern "C" {
 #define _INSTRUMENTED_POP_JUMP_IF_NONE INSTRUMENTED_POP_JUMP_IF_NONE
 #define _INSTRUMENTED_POP_JUMP_IF_NOT_NONE INSTRUMENTED_POP_JUMP_IF_NOT_NONE
 #define _INSTRUMENTED_POP_JUMP_IF_TRUE INSTRUMENTED_POP_JUMP_IF_TRUE
-#define _IS_NONE 415
+#define _IS_NONE 418
 #define _IS_OP IS_OP
-#define _ITER_CHECK_LIST 416
-#define _ITER_CHECK_RANGE 417
-#define _ITER_CHECK_TUPLE 418
-#define _ITER_JUMP_LIST 419
-#define _ITER_JUMP_RANGE 420
-#define _ITER_JUMP_TUPLE 421
-#define _ITER_NEXT_LIST 422
-#define _ITER_NEXT_LIST_TIER_TWO 423
-#define _ITER_NEXT_RANGE 424
-#define _ITER_NEXT_TUPLE 425
-#define _JUMP_TO_TOP 426
+#define _ITER_CHECK_LIST 419
+#define _ITER_CHECK_RANGE 420
+#define _ITER_CHECK_TUPLE 421
+#define _ITER_JUMP_LIST 422
+#define _ITER_JUMP_RANGE 423
+#define _ITER_JUMP_TUPLE 424
+#define _ITER_NEXT_LIST 425
+#define _ITER_NEXT_LIST_TIER_TWO 426
+#define _ITER_NEXT_RANGE 427
+#define _ITER_NEXT_TUPLE 428
+#define _JUMP_TO_TOP 429
 #define _LIST_APPEND LIST_APPEND
 #define _LIST_EXTEND LIST_EXTEND
-#define _LOAD_ATTR 427
-#define _LOAD_ATTR_CLASS 428
+#define _LOAD_ATTR 430
+#define _LOAD_ATTR_CLASS 431
 #define _LOAD_ATTR_GETATTRIBUTE_OVERRIDDEN LOAD_ATTR_GETATTRIBUTE_OVERRIDDEN
-#define _LOAD_ATTR_INSTANCE_VALUE 429
-#define _LOAD_ATTR_METHOD_LAZY_DICT 430
-#define _LOAD_ATTR_METHOD_NO_DICT 431
-#define _LOAD_ATTR_METHOD_WITH_VALUES 432
-#define _LOAD_ATTR_MODULE 433
-#define _LOAD_ATTR_NONDESCRIPTOR_NO_DICT 434
-#define _LOAD_ATTR_NONDESCRIPTOR_WITH_VALUES 435
-#define _LOAD_ATTR_PROPERTY_FRAME 436
-#define _LOAD_ATTR_SLOT 437
-#define _LOAD_ATTR_WITH_HINT 438
+#define _LOAD_ATTR_INSTANCE_VALUE 432
+#define _LOAD_ATTR_METHOD_LAZY_DICT 433
+#define _LOAD_ATTR_METHOD_NO_DICT 434
+#define _LOAD_ATTR_METHOD_WITH_VALUES 435
+#define _LOAD_ATTR_MODULE 436
+#define _LOAD_ATTR_NONDESCRIPTOR_NO_DICT 437
+#define _LOAD_ATTR_NONDESCRIPTOR_WITH_VALUES 438
+#define _LOAD_ATTR_PROPERTY_FRAME 439
+#define _LOAD_ATTR_SLOT 440
+#define _LOAD_ATTR_WITH_HINT 441
 #define _LOAD_BUILD_CLASS LOAD_BUILD_CLASS
-#define _LOAD_BYTECODE 439
+#define _LOAD_BYTECODE 442
 #define _LOAD_COMMON_CONSTANT LOAD_COMMON_CONSTANT
 #define _LOAD_CONST LOAD_CONST
 #define _LOAD_CONST_IMMORTAL LOAD_CONST_IMMORTAL
-#define _LOAD_CONST_INLINE 440
-#define _LOAD_CONST_INLINE_BORROW 441
+#define _LOAD_CONST_INLINE 443
+#define _LOAD_CONST_INLINE_BORROW 444
 #define _LOAD_CONST_MORTAL LOAD_CONST_MORTAL
 #define _LOAD_DEREF LOAD_DEREF
-#define _LOAD_FAST 442
-#define _LOAD_FAST_0 443
-#define _LOAD_FAST_1 444
-#define _LOAD_FAST_2 445
-#define _LOAD_FAST_3 446
-#define _LOAD_FAST_4 447
-#define _LOAD_FAST_5 448
-#define _LOAD_FAST_6 449
-#define _LOAD_FAST_7 450
+#define _LOAD_FAST 445
+#define _LOAD_FAST_0 446
+#define _LOAD_FAST_1 447
+#define _LOAD_FAST_2 448
+#define _LOAD_FAST_3 449
+#define _LOAD_FAST_4 450
+#define _LOAD_FAST_5 451
+#define _LOAD_FAST_6 452
+#define _LOAD_FAST_7 453
 #define _LOAD_FAST_AND_CLEAR LOAD_FAST_AND_CLEAR
-#define _LOAD_FAST_BORROW 451
-#define _LOAD_FAST_BORROW_0 452
-#define _LOAD_FAST_BORROW_1 453
-#define _LOAD_FAST_BORROW_2 454
-#define _LOAD_FAST_BORROW_3 455
-#define _LOAD_FAST_BORROW_4 456
-#define _LOAD_FAST_BORROW_5 457
-#define _LOAD_FAST_BORROW_6 458
-#define _LOAD_FAST_BORROW_7 459
+#define _LOAD_FAST_BORROW 454
+#define _LOAD_FAST_BORROW_0 455
+#define _LOAD_FAST_BORROW_1 456
+#define _LOAD_FAST_BORROW_2 457
+#define _LOAD_FAST_BORROW_3 458
+#define _LOAD_FAST_BORROW_4 459
+#define _LOAD_FAST_BORROW_5 460
+#define _LOAD_FAST_BORROW_6 461
+#define _LOAD_FAST_BORROW_7 462
 #define _LOAD_FAST_BORROW_LOAD_FAST_BORROW LOAD_FAST_BORROW_LOAD_FAST_BORROW
 #define _LOAD_FAST_CHECK LOAD_FAST_CHECK
 #define _LOAD_FAST_LOAD_FAST LOAD_FAST_LOAD_FAST
 #define _LOAD_FROM_DICT_OR_DEREF LOAD_FROM_DICT_OR_DEREF
 #define _LOAD_FROM_DICT_OR_GLOBALS LOAD_FROM_DICT_OR_GLOBALS
-#define _LOAD_GLOBAL 460
-#define _LOAD_GLOBAL_BUILTINS 461
-#define _LOAD_GLOBAL_MODULE 462
+#define _LOAD_GLOBAL 463
+#define _LOAD_GLOBAL_BUILTINS 464
+#define _LOAD_GLOBAL_MODULE 465
 #define _LOAD_LOCALS LOAD_LOCALS
 #define _LOAD_NAME LOAD_NAME
-#define _LOAD_SMALL_INT 463
-#define _LOAD_SMALL_INT_0 464
-#define _LOAD_SMALL_INT_1 465
-#define _LOAD_SMALL_INT_2 466
-#define _LOAD_SMALL_INT_3 467
-#define _LOAD_SPECIAL 468
+#define _LOAD_SMALL_INT 466
+#define _LOAD_SMALL_INT_0 467
+#define _LOAD_SMALL_INT_1 468
+#define _LOAD_SMALL_INT_2 469
+#define _LOAD_SMALL_INT_3 470
+#define _LOAD_SPECIAL 471
 #define _LOAD_SUPER_ATTR_ATTR LOAD_SUPER_ATTR_ATTR
 #define _LOAD_SUPER_ATTR_METHOD LOAD_SUPER_ATTR_METHOD
-#define _MAKE_CALLARGS_A_TUPLE 469
+#define _MAKE_CALLARGS_A_TUPLE 472
 #define _MAKE_CELL MAKE_CELL
 #define _MAKE_FUNCTION MAKE_FUNCTION
-#define _MAKE_WARM 470
+#define _MAKE_WARM 473
 #define _MAP_ADD MAP_ADD
 #define _MATCH_CLASS MATCH_CLASS
 #define _MATCH_KEYS MATCH_KEYS
 #define _MATCH_MAPPING MATCH_MAPPING
 #define _MATCH_SEQUENCE MATCH_SEQUENCE
-#define _MAYBE_EXPAND_METHOD 471
-#define _MAYBE_EXPAND_METHOD_KW 472
-#define _MONITOR_CALL 473
-#define _MONITOR_CALL_KW 474
-#define _MONITOR_JUMP_BACKWARD 475
-#define _MONITOR_RESUME 476
+#define _MAYBE_EXPAND_METHOD 474
+#define _MAYBE_EXPAND_METHOD_KW 475
+#define _MONITOR_CALL 476
+#define _MONITOR_CALL_KW 477
+#define _MONITOR_JUMP_BACKWARD 478
+#define _MONITOR_RESUME 479
 #define _NOP NOP
 #define _POP_EXCEPT POP_EXCEPT
-#define _POP_JUMP_IF_FALSE 477
-#define _POP_JUMP_IF_TRUE 478
+#define _POP_JUMP_IF_FALSE 480
+#define _POP_JUMP_IF_TRUE 481
 #define _POP_TOP POP_TOP
-#define _POP_TOP_LOAD_CONST_INLINE 479
-#define _POP_TOP_LOAD_CONST_INLINE_BORROW 480
-#define _POP_TWO_LOAD_CONST_INLINE_BORROW 481
+#define _POP_TOP_LOAD_CONST_INLINE 482
+#define _POP_TOP_LOAD_CONST_INLINE_BORROW 483
+#define _POP_TWO_LOAD_CONST_INLINE_BORROW 484
 #define _PUSH_EXC_INFO PUSH_EXC_INFO
-#define _PUSH_FRAME 482
+#define _PUSH_FRAME 485
 #define _PUSH_NULL PUSH_NULL
-#define _PUSH_NULL_CONDITIONAL 483
-#define _PY_FRAME_GENERAL 484
-#define _PY_FRAME_KW 485
-#define _QUICKEN_RESUME 486
-#define _REPLACE_WITH_TRUE 487
+#define _PUSH_NULL_CONDITIONAL 486
+#define _PY_FRAME_GENERAL 487
+#define _PY_FRAME_KW 488
+#define _QUICKEN_RESUME 489
+#define _REPLACE_WITH_TRUE 490
 #define _RESUME_CHECK RESUME_CHECK
 #define _RETURN_GENERATOR RETURN_GENERATOR
 #define _RETURN_VALUE RETURN_VALUE
-#define _SAVE_RETURN_OFFSET 488
-#define _SEND 489
-#define _SEND_GEN_FRAME 490
+#define _SAVE_RETURN_OFFSET 491
+#define _SEND 492
+#define _SEND_GEN_FRAME 493
 #define _SETUP_ANNOTATIONS SETUP_ANNOTATIONS
 #define _SET_ADD SET_ADD
 #define _SET_FUNCTION_ATTRIBUTE SET_FUNCTION_ATTRIBUTE
 #define _SET_UPDATE SET_UPDATE
-#define _START_EXECUTOR 491
-#define _STORE_ATTR 492
-#define _STORE_ATTR_INSTANCE_VALUE 493
-#define _STORE_ATTR_SLOT 494
-#define _STORE_ATTR_WITH_HINT 495
+#define _START_EXECUTOR 494
+#define _STORE_ATTR 495
+#define _STORE_ATTR_INSTANCE_VALUE 496
+#define _STORE_ATTR_SLOT 497
+#define _STORE_ATTR_WITH_HINT 498
 #define _STORE_DEREF STORE_DEREF
-#define _STORE_FAST 496
-#define _STORE_FAST_0 497
-#define _STORE_FAST_1 498
-#define _STORE_FAST_2 499
-#define _STORE_FAST_3 500
-#define _STORE_FAST_4 501
-#define _STORE_FAST_5 502
-#define _STORE_FAST_6 503
-#define _STORE_FAST_7 504
+#define _STORE_FAST 499
+#define _STORE_FAST_0 500
+#define _STORE_FAST_1 501
+#define _STORE_FAST_2 502
+#define _STORE_FAST_3 503
+#define _STORE_FAST_4 504
+#define _STORE_FAST_5 505
+#define _STORE_FAST_6 506
+#define _STORE_FAST_7 507
 #define _STORE_FAST_LOAD_FAST STORE_FAST_LOAD_FAST
 #define _STORE_FAST_STORE_FAST STORE_FAST_STORE_FAST
 #define _STORE_GLOBAL STORE_GLOBAL
 #define _STORE_NAME STORE_NAME
-#define _STORE_SLICE 505
-#define _STORE_SUBSCR 506
-#define _STORE_SUBSCR_DICT 507
-#define _STORE_SUBSCR_LIST_INT 508
+#define _STORE_SLICE 508
+#define _STORE_SUBSCR 509
+#define _STORE_SUBSCR_DICT 510
+#define _STORE_SUBSCR_LIST_INT 511
 #define _SWAP SWAP
-#define _TIER2_RESUME_CHECK 509
-#define _TO_BOOL 510
+#define _TIER2_RESUME_CHECK 512
+#define _TO_BOOL 513
 #define _TO_BOOL_BOOL TO_BOOL_BOOL
 #define _TO_BOOL_INT TO_BOOL_INT
-#define _TO_BOOL_LIST 511
+#define _TO_BOOL_LIST 514
 #define _TO_BOOL_NONE TO_BOOL_NONE
-#define _TO_BOOL_STR 512
+#define _TO_BOOL_STR 515
 #define _UNARY_INVERT UNARY_INVERT
 #define _UNARY_NEGATIVE UNARY_NEGATIVE
 #define _UNARY_NOT UNARY_NOT
 #define _UNPACK_EX UNPACK_EX
-#define _UNPACK_SEQUENCE 513
-#define _UNPACK_SEQUENCE_LIST 514
-#define _UNPACK_SEQUENCE_TUPLE 515
-#define _UNPACK_SEQUENCE_TWO_TUPLE 516
+#define _UNPACK_SEQUENCE 516
+#define _UNPACK_SEQUENCE_LIST 517
+#define _UNPACK_SEQUENCE_TUPLE 518
+#define _UNPACK_SEQUENCE_TWO_TUPLE 519
 #define _WITH_EXCEPT_START WITH_EXCEPT_START
 #define _YIELD_VALUE YIELD_VALUE
-#define MAX_UOP_ID 516
+#define MAX_UOP_ID 519
 
 #ifdef __cplusplus
 }
diff --git a/Include/internal/pycore_uop_metadata.h b/Include/internal/pycore_uop_metadata.h
index 912b1e56692..88a2e538447 100644
--- a/Include/internal/pycore_uop_metadata.h
+++ b/Include/internal/pycore_uop_metadata.h
@@ -247,6 +247,7 @@ const uint16_t _PyUop_Flags[MAX_UOP_ID+1] = {
     [_INIT_CALL_PY_EXACT_ARGS] = HAS_ARG_FLAG | HAS_PURE_FLAG,
     [_PUSH_FRAME] = 0,
     [_GUARD_NOS_NULL] = HAS_DEOPT_FLAG,
+    [_GUARD_THIRD_NULL] = HAS_DEOPT_FLAG,
     [_GUARD_CALLABLE_TYPE_1] = HAS_DEOPT_FLAG,
     [_CALL_TYPE_1] = HAS_ARG_FLAG | HAS_ESCAPES_FLAG,
     [_GUARD_CALLABLE_STR_1] = HAS_DEOPT_FLAG,
@@ -262,7 +263,8 @@ const uint16_t _PyUop_Flags[MAX_UOP_ID+1] = {
     [_CALL_BUILTIN_FAST_WITH_KEYWORDS] = HAS_ARG_FLAG | HAS_DEOPT_FLAG | HAS_ERROR_FLAG | HAS_ESCAPES_FLAG,
     [_GUARD_CALLABLE_LEN] = HAS_DEOPT_FLAG,
     [_CALL_LEN] = HAS_ERROR_FLAG | HAS_ERROR_NO_POP_FLAG | HAS_ESCAPES_FLAG,
-    [_CALL_ISINSTANCE] = HAS_ARG_FLAG | HAS_DEOPT_FLAG | HAS_ERROR_FLAG | HAS_ERROR_NO_POP_FLAG | HAS_ESCAPES_FLAG,
+    [_GUARD_CALLABLE_ISINSTANCE] = HAS_DEOPT_FLAG,
+    [_CALL_ISINSTANCE] = HAS_ERROR_FLAG | HAS_ERROR_NO_POP_FLAG | HAS_ESCAPES_FLAG,
     [_CALL_LIST_APPEND] = HAS_ARG_FLAG | HAS_DEOPT_FLAG | HAS_ERROR_FLAG | HAS_ESCAPES_FLAG,
     [_CALL_METHOD_DESCRIPTOR_O] = HAS_ARG_FLAG | HAS_EXIT_FLAG | HAS_ERROR_FLAG | HAS_ESCAPES_FLAG,
     [_CALL_METHOD_DESCRIPTOR_FAST_WITH_KEYWORDS] = HAS_ARG_FLAG | HAS_EXIT_FLAG | HAS_ERROR_FLAG | HAS_ESCAPES_FLAG,
@@ -425,6 +427,7 @@ const char *const _PyOpcode_uop_name[MAX_UOP_ID+1] = {
     [_GET_LEN] = "_GET_LEN",
     [_GET_YIELD_FROM_ITER] = "_GET_YIELD_FROM_ITER",
     [_GUARD_BINARY_OP_EXTEND] = "_GUARD_BINARY_OP_EXTEND",
+    [_GUARD_CALLABLE_ISINSTANCE] = "_GUARD_CALLABLE_ISINSTANCE",
     [_GUARD_CALLABLE_LEN] = "_GUARD_CALLABLE_LEN",
     [_GUARD_CALLABLE_STR_1] = "_GUARD_CALLABLE_STR_1",
     [_GUARD_CALLABLE_TUPLE_1] = "_GUARD_CALLABLE_TUPLE_1",
@@ -447,6 +450,7 @@ const char *const _PyOpcode_uop_name[MAX_UOP_ID+1] = {
     [_GUARD_NOT_EXHAUSTED_LIST] = "_GUARD_NOT_EXHAUSTED_LIST",
     [_GUARD_NOT_EXHAUSTED_RANGE] = "_GUARD_NOT_EXHAUSTED_RANGE",
     [_GUARD_NOT_EXHAUSTED_TUPLE] = "_GUARD_NOT_EXHAUSTED_TUPLE",
+    [_GUARD_THIRD_NULL] = "_GUARD_THIRD_NULL",
     [_GUARD_TOS_ANY_SET] = "_GUARD_TOS_ANY_SET",
     [_GUARD_TOS_DICT] = "_GUARD_TOS_DICT",
     [_GUARD_TOS_FLOAT] = "_GUARD_TOS_FLOAT",
@@ -1068,6 +1072,8 @@ int _PyUop_num_popped(int opcode, int oparg)
             return 1;
         case _GUARD_NOS_NULL:
             return 0;
+        case _GUARD_THIRD_NULL:
+            return 0;
         case _GUARD_CALLABLE_TYPE_1:
             return 0;
         case _CALL_TYPE_1:
@@ -1098,8 +1104,10 @@ int _PyUop_num_popped(int opcode, int oparg)
             return 0;
         case _CALL_LEN:
             return 3;
+        case _GUARD_CALLABLE_ISINSTANCE:
+            return 0;
         case _CALL_ISINSTANCE:
-            return 2 + oparg;
+            return 4;
         case _CALL_LIST_APPEND:
             return 3;
         case _CALL_METHOD_DESCRIPTOR_O:
diff --git a/Lib/test/test_capi/test_opt.py b/Lib/test/test_capi/test_opt.py
index ba7bcb4540a..651148336f7 100644
--- a/Lib/test/test_capi/test_opt.py
+++ b/Lib/test/test_capi/test_opt.py
@@ -1942,6 +1942,23 @@ class TestUopsOptimization(unittest.TestCase):
         self.assertNotIn("_COMPARE_OP_INT", uops)
         self.assertNotIn("_GUARD_IS_TRUE_POP", uops)
 
+    def test_call_isinstance_guards_removed(self):
+        def testfunc(n):
+            x = 0
+            for _ in range(n):
+                y = isinstance(42, int)
+                if y:
+                    x += 1
+            return x
+
+        res, ex = self._run_with_optimizer(testfunc, TIER2_THRESHOLD)
+        self.assertEqual(res, TIER2_THRESHOLD)
+        self.assertIsNotNone(ex)
+        uops = get_opnames(ex)
+        self.assertIn("_CALL_ISINSTANCE", uops)
+        self.assertNotIn("_GUARD_THIRD_NULL", uops)
+        self.assertNotIn("_GUARD_CALLABLE_ISINSTANCE", uops)
+
 
 def global_identity(x):
     return x
diff --git a/Misc/NEWS.d/next/Core_and_Builtins/2025-05-03-13-36-01.gh-issue-131798.U4_QEJ.rst b/Misc/NEWS.d/next/Core_and_Builtins/2025-05-03-13-36-01.gh-issue-131798.U4_QEJ.rst
new file mode 100644
index 00000000000..ca8eb999ae5
--- /dev/null
+++ b/Misc/NEWS.d/next/Core_and_Builtins/2025-05-03-13-36-01.gh-issue-131798.U4_QEJ.rst
@@ -0,0 +1,2 @@
+Split ``CALL_ISINSTANCE`` into several uops, allowing the JIT to remove some
+of them.
diff --git a/Python/bytecodes.c b/Python/bytecodes.c
index 6a076662640..42e4f581894 100644
--- a/Python/bytecodes.c
+++ b/Python/bytecodes.c
@@ -4041,6 +4041,10 @@ dummy_func(
             DEOPT_IF(!PyStackRef_IsNull(null));
         }
 
+        op(_GUARD_THIRD_NULL, (null, unused, unused -- null, unused, unused)) {
+            DEOPT_IF(!PyStackRef_IsNull(null));
+        }
+
         op(_GUARD_CALLABLE_TYPE_1, (callable, unused, unused -- callable, unused, unused)) {
             PyObject *callable_o = PyStackRef_AsPyObjectBorrow(callable);
             DEOPT_IF(callable_o != (PyObject *)&PyType_Type);
@@ -4359,31 +4363,37 @@ dummy_func(
             res = PyStackRef_FromPyObjectSteal(res_o);
         }
 
-        inst(CALL_ISINSTANCE, (unused/1, unused/2, callable, self_or_null, args[oparg] -- res)) {
-            /* isinstance(o, o2) */
+        op(_GUARD_CALLABLE_ISINSTANCE, (callable, unused, unused, unused -- callable, unused, unused, unused)) {
             PyObject *callable_o = PyStackRef_AsPyObjectBorrow(callable);
-
-            int total_args = oparg;
-            _PyStackRef *arguments = args;
-            if (!PyStackRef_IsNull(self_or_null)) {
-                arguments--;
-                total_args++;
-            }
-            DEOPT_IF(total_args != 2);
             PyInterpreterState *interp = tstate->interp;
             DEOPT_IF(callable_o != interp->callable_cache.isinstance);
+        }
+
+        op(_CALL_ISINSTANCE, (callable, null, instance, cls -- res)) {
+            /* isinstance(o, o2) */
             STAT_INC(CALL, hit);
-            _PyStackRef cls_stackref = arguments[1];
-            _PyStackRef inst_stackref = arguments[0];
-            int retval = PyObject_IsInstance(PyStackRef_AsPyObjectBorrow(inst_stackref), PyStackRef_AsPyObjectBorrow(cls_stackref));
+            PyObject *inst_o = PyStackRef_AsPyObjectBorrow(instance);
+            PyObject *cls_o = PyStackRef_AsPyObjectBorrow(cls);
+            int retval = PyObject_IsInstance(inst_o, cls_o);
             if (retval < 0) {
                 ERROR_NO_POP();
             }
+            (void)null; // Silence compiler warnings about unused variables
+            PyStackRef_CLOSE(cls);
+            PyStackRef_CLOSE(instance);
+            DEAD(null);
+            PyStackRef_CLOSE(callable);
             res = retval ? PyStackRef_True : PyStackRef_False;
             assert((!PyStackRef_IsNull(res)) ^ (_PyErr_Occurred(tstate) != NULL));
-            DECREF_INPUTS();
         }
 
+        macro(CALL_ISINSTANCE) =
+            unused/1 +
+            unused/2 +
+            _GUARD_THIRD_NULL +
+            _GUARD_CALLABLE_ISINSTANCE +
+            _CALL_ISINSTANCE;
+
         // This is secretly a super-instruction
         inst(CALL_LIST_APPEND, (unused/1, unused/2, callable, self, arg -- )) {
             assert(oparg == 1);
diff --git a/Python/executor_cases.c.h b/Python/executor_cases.c.h
index 3e51ac41fa3..41c9bd5ba70 100644
--- a/Python/executor_cases.c.h
+++ b/Python/executor_cases.c.h
@@ -5276,6 +5276,16 @@
             break;
         }
 
+        case _GUARD_THIRD_NULL: {
+            _PyStackRef null;
+            null = stack_pointer[-3];
+            if (!PyStackRef_IsNull(null)) {
+                UOP_STAT_INC(uopcode, miss);
+                JUMP_TO_JUMP_TARGET();
+            }
+            break;
+        }
+
         case _GUARD_CALLABLE_TYPE_1: {
             _PyStackRef callable;
             callable = stack_pointer[-3];
@@ -5855,58 +5865,57 @@
             break;
         }
 
-        case _CALL_ISINSTANCE: {
-            _PyStackRef *args;
-            _PyStackRef self_or_null;
+        case _GUARD_CALLABLE_ISINSTANCE: {
             _PyStackRef callable;
-            _PyStackRef res;
-            oparg = CURRENT_OPARG();
-            args = &stack_pointer[-oparg];
-            self_or_null = stack_pointer[-1 - oparg];
-            callable = stack_pointer[-2 - oparg];
+            callable = stack_pointer[-4];
             PyObject *callable_o = PyStackRef_AsPyObjectBorrow(callable);
-            int total_args = oparg;
-            _PyStackRef *arguments = args;
-            if (!PyStackRef_IsNull(self_or_null)) {
-                arguments--;
-                total_args++;
-            }
-            if (total_args != 2) {
-                UOP_STAT_INC(uopcode, miss);
-                JUMP_TO_JUMP_TARGET();
-            }
             PyInterpreterState *interp = tstate->interp;
             if (callable_o != interp->callable_cache.isinstance) {
                 UOP_STAT_INC(uopcode, miss);
                 JUMP_TO_JUMP_TARGET();
             }
+            break;
+        }
+
+        case _CALL_ISINSTANCE: {
+            _PyStackRef cls;
+            _PyStackRef instance;
+            _PyStackRef null;
+            _PyStackRef callable;
+            _PyStackRef res;
+            cls = stack_pointer[-1];
+            instance = stack_pointer[-2];
+            null = stack_pointer[-3];
+            callable = stack_pointer[-4];
             STAT_INC(CALL, hit);
-            _PyStackRef cls_stackref = arguments[1];
-            _PyStackRef inst_stackref = arguments[0];
+            PyObject *inst_o = PyStackRef_AsPyObjectBorrow(instance);
+            PyObject *cls_o = PyStackRef_AsPyObjectBorrow(cls);
             _PyFrame_SetStackPointer(frame, stack_pointer);
-            int retval = PyObject_IsInstance(PyStackRef_AsPyObjectBorrow(inst_stackref), PyStackRef_AsPyObjectBorrow(cls_stackref));
+            int retval = PyObject_IsInstance(inst_o, cls_o);
             stack_pointer = _PyFrame_GetStackPointer(frame);
             if (retval < 0) {
                 JUMP_TO_ERROR();
             }
-            res = retval ? PyStackRef_True : PyStackRef_False;
-            assert((!PyStackRef_IsNull(res)) ^ (_PyErr_Occurred(tstate) != NULL));
+            (void)null;
+            stack_pointer += -1;
+            assert(WITHIN_STACK_BOUNDS());
             _PyFrame_SetStackPointer(frame, stack_pointer);
-            _PyStackRef tmp = callable;
-            callable = res;
-            stack_pointer[-2 - oparg] = callable;
-            PyStackRef_CLOSE(tmp);
-            for (int _i = oparg; --_i >= 0;) {
-                tmp = args[_i];
-                args[_i] = PyStackRef_NULL;
-                PyStackRef_CLOSE(tmp);
-            }
-            tmp = self_or_null;
-            self_or_null = PyStackRef_NULL;
-            stack_pointer[-1 - oparg] = self_or_null;
-            PyStackRef_XCLOSE(tmp);
+            PyStackRef_CLOSE(cls);
             stack_pointer = _PyFrame_GetStackPointer(frame);
-            stack_pointer += -1 - oparg;
+            stack_pointer += -1;
+            assert(WITHIN_STACK_BOUNDS());
+            _PyFrame_SetStackPointer(frame, stack_pointer);
+            PyStackRef_CLOSE(instance);
+            stack_pointer = _PyFrame_GetStackPointer(frame);
+            stack_pointer += -2;
+            assert(WITHIN_STACK_BOUNDS());
+            _PyFrame_SetStackPointer(frame, stack_pointer);
+            PyStackRef_CLOSE(callable);
+            stack_pointer = _PyFrame_GetStackPointer(frame);
+            res = retval ? PyStackRef_True : PyStackRef_False;
+            assert((!PyStackRef_IsNull(res)) ^ (_PyErr_Occurred(tstate) != NULL));
+            stack_pointer[0] = res;
+            stack_pointer += 1;
             assert(WITHIN_STACK_BOUNDS());
             break;
         }
diff --git a/Python/generated_cases.c.h b/Python/generated_cases.c.h
index 7e8b05b747e..b3f2a2067f7 100644
--- a/Python/generated_cases.c.h
+++ b/Python/generated_cases.c.h
@@ -2777,60 +2777,67 @@
             next_instr += 4;
             INSTRUCTION_STATS(CALL_ISINSTANCE);
             static_assert(INLINE_CACHE_ENTRIES_CALL == 3, "incorrect cache size");
+            _PyStackRef null;
             _PyStackRef callable;
-            _PyStackRef self_or_null;
-            _PyStackRef *args;
+            _PyStackRef instance;
+            _PyStackRef cls;
             _PyStackRef res;
             /* Skip 1 cache entry */
             /* Skip 2 cache entries */
-            args = &stack_pointer[-oparg];
-            self_or_null = stack_pointer[-1 - oparg];
-            callable = stack_pointer[-2 - oparg];
-            PyObject *callable_o = PyStackRef_AsPyObjectBorrow(callable);
-            int total_args = oparg;
-            _PyStackRef *arguments = args;
-            if (!PyStackRef_IsNull(self_or_null)) {
-                arguments--;
-                total_args++;
-            }
-            if (total_args != 2) {
-                UPDATE_MISS_STATS(CALL);
-                assert(_PyOpcode_Deopt[opcode] == (CALL));
-                JUMP_TO_PREDICTED(CALL);
-            }
-            PyInterpreterState *interp = tstate->interp;
-            if (callable_o != interp->callable_cache.isinstance) {
-                UPDATE_MISS_STATS(CALL);
-                assert(_PyOpcode_Deopt[opcode] == (CALL));
-                JUMP_TO_PREDICTED(CALL);
+            // _GUARD_THIRD_NULL
+            {
+                null = stack_pointer[-3];
+                if (!PyStackRef_IsNull(null)) {
+                    UPDATE_MISS_STATS(CALL);
+                    assert(_PyOpcode_Deopt[opcode] == (CALL));
+                    JUMP_TO_PREDICTED(CALL);
+                }
             }
-            STAT_INC(CALL, hit);
-            _PyStackRef cls_stackref = arguments[1];
-            _PyStackRef inst_stackref = arguments[0];
-            _PyFrame_SetStackPointer(frame, stack_pointer);
-            int retval = PyObject_IsInstance(PyStackRef_AsPyObjectBorrow(inst_stackref), PyStackRef_AsPyObjectBorrow(cls_stackref));
-            stack_pointer = _PyFrame_GetStackPointer(frame);
-            if (retval < 0) {
-                JUMP_TO_LABEL(error);
+            // _GUARD_CALLABLE_ISINSTANCE
+            {
+                callable = stack_pointer[-4];
+                PyObject *callable_o = PyStackRef_AsPyObjectBorrow(callable);
+                PyInterpreterState *interp = tstate->interp;
+                if (callable_o != interp->callable_cache.isinstance) {
+                    UPDATE_MISS_STATS(CALL);
+                    assert(_PyOpcode_Deopt[opcode] == (CALL));
+                    JUMP_TO_PREDICTED(CALL);
+                }
             }
-            res = retval ? PyStackRef_True : PyStackRef_False;
-            assert((!PyStackRef_IsNull(res)) ^ (_PyErr_Occurred(tstate) != NULL));
-            _PyFrame_SetStackPointer(frame, stack_pointer);
-            _PyStackRef tmp = callable;
-            callable = res;
-            stack_pointer[-2 - oparg] = callable;
-            PyStackRef_CLOSE(tmp);
-            for (int _i = oparg; --_i >= 0;) {
-                tmp = args[_i];
-                args[_i] = PyStackRef_NULL;
-                PyStackRef_CLOSE(tmp);
+            // _CALL_ISINSTANCE
+            {
+                cls = stack_pointer[-1];
+                instance = stack_pointer[-2];
+                STAT_INC(CALL, hit);
+                PyObject *inst_o = PyStackRef_AsPyObjectBorrow(instance);
+                PyObject *cls_o = PyStackRef_AsPyObjectBorrow(cls);
+                _PyFrame_SetStackPointer(frame, stack_pointer);
+                int retval = PyObject_IsInstance(inst_o, cls_o);
+                stack_pointer = _PyFrame_GetStackPointer(frame);
+                if (retval < 0) {
+                    JUMP_TO_LABEL(error);
+                }
+                (void)null;
+                stack_pointer += -1;
+                assert(WITHIN_STACK_BOUNDS());
+                _PyFrame_SetStackPointer(frame, stack_pointer);
+                PyStackRef_CLOSE(cls);
+                stack_pointer = _PyFrame_GetStackPointer(frame);
+                stack_pointer += -1;
+                assert(WITHIN_STACK_BOUNDS());
+                _PyFrame_SetStackPointer(frame, stack_pointer);
+                PyStackRef_CLOSE(instance);
+                stack_pointer = _PyFrame_GetStackPointer(frame);
+                stack_pointer += -2;
+                assert(WITHIN_STACK_BOUNDS());
+                _PyFrame_SetStackPointer(frame, stack_pointer);
+                PyStackRef_CLOSE(callable);
+                stack_pointer = _PyFrame_GetStackPointer(frame);
+                res = retval ? PyStackRef_True : PyStackRef_False;
+                assert((!PyStackRef_IsNull(res)) ^ (_PyErr_Occurred(tstate) != NULL));
             }
-            tmp = self_or_null;
-            self_or_null = PyStackRef_NULL;
-            stack_pointer[-1 - oparg] = self_or_null;
-            PyStackRef_XCLOSE(tmp);
-            stack_pointer = _PyFrame_GetStackPointer(frame);
-            stack_pointer += -1 - oparg;
+            stack_pointer[0] = res;
+            stack_pointer += 1;
             assert(WITHIN_STACK_BOUNDS());
             DISPATCH();
         }
diff --git a/Python/optimizer_bytecodes.c b/Python/optimizer_bytecodes.c
index 238c370f475..7c160cdcb0c 100644
--- a/Python/optimizer_bytecodes.c
+++ b/Python/optimizer_bytecodes.c
@@ -1067,6 +1067,13 @@ dummy_func(void) {
         sym_set_null(null);
     }
 
+    op(_GUARD_THIRD_NULL, (null, unused, unused -- null, unused, unused)) {
+        if (sym_is_null(null)) {
+            REPLACE_OP(this_instr, _NOP, 0, 0);
+        }
+        sym_set_null(null);
+    }
+
     op(_GUARD_CALLABLE_TYPE_1, (callable, unused, unused -- callable, unused, unused)) {
         if (sym_get_const(ctx, callable) == (PyObject *)&PyType_Type) {
             REPLACE_OP(this_instr, _NOP, 0, 0);
@@ -1100,6 +1107,14 @@ dummy_func(void) {
         sym_set_const(callable, len);
     }
 
+    op(_GUARD_CALLABLE_ISINSTANCE, (callable, unused, unused, unused -- callable, unused, unused, unused)) {
+        PyObject *isinstance = _PyInterpreterState_GET()->callable_cache.isinstance;
+        if (sym_get_const(ctx, callable) == isinstance) {
+            REPLACE_OP(this_instr, _NOP, 0, 0);
+        }
+        sym_set_const(callable, isinstance);
+    }
+
 // END BYTECODES //
 
 }
diff --git a/Python/optimizer_cases.c.h b/Python/optimizer_cases.c.h
index 4c49d106fa8..deb912662e4 100644
--- a/Python/optimizer_cases.c.h
+++ b/Python/optimizer_cases.c.h
@@ -1935,6 +1935,16 @@
             break;
         }
 
+        case _GUARD_THIRD_NULL: {
+            JitOptSymbol *null;
+            null = stack_pointer[-3];
+            if (sym_is_null(null)) {
+                REPLACE_OP(this_instr, _NOP, 0, 0);
+            }
+            sym_set_null(null);
+            break;
+        }
+
         case _GUARD_CALLABLE_TYPE_1: {
             JitOptSymbol *callable;
             callable = stack_pointer[-3];
@@ -2102,11 +2112,22 @@
             break;
         }
 
+        case _GUARD_CALLABLE_ISINSTANCE: {
+            JitOptSymbol *callable;
+            callable = stack_pointer[-4];
+            PyObject *isinstance = _PyInterpreterState_GET()->callable_cache.isinstance;
+            if (sym_get_const(ctx, callable) == isinstance) {
+                REPLACE_OP(this_instr, _NOP, 0, 0);
+            }
+            sym_set_const(callable, isinstance);
+            break;
+        }
+
         case _CALL_ISINSTANCE: {
             JitOptSymbol *res;
             res = sym_new_not_null(ctx);
-            stack_pointer[-2 - oparg] = res;
-            stack_pointer += -1 - oparg;
+            stack_pointer[-4] = res;
+            stack_pointer += -3;
             assert(WITHIN_STACK_BOUNDS());
             break;
         }
diff --git a/Python/specialize.c b/Python/specialize.c
index bbe725c8ec8..06995d46d8b 100644
--- a/Python/specialize.c
+++ b/Python/specialize.c
@@ -2158,7 +2158,7 @@ specialize_c_call(PyObject *callable, _Py_CODEUNIT *instr, int nargs)
             if (nargs == 2) {
                 /* isinstance(o1, o2) */
                 PyInterpreterState *interp = _PyInterpreterState_GET();
-                if (callable == interp->callable_cache.isinstance) {
+                if (callable == interp->callable_cache.isinstance && instr->op.arg == 2) {
                     specialize(instr, CALL_ISINSTANCE);
                     return 0;
                 }