diff --git a/Lib/test/test_list.py b/Lib/test/test_list.py
index 4d2d54705fc..ad7accf2099 100644
--- a/Lib/test/test_list.py
+++ b/Lib/test/test_list.py
@@ -299,6 +299,15 @@ class ListTest(list_tests.CommonTest):
         lst = [X(), X()]
         X() in lst
 
+    def test_tier2_invalidates_iterator(self):
+        # GH-121012
+        for _ in range(100):
+            a = [1, 2, 3]
+            it = iter(a)
+            for _ in it:
+                pass
+            a.append(4)
+            self.assertEqual(list(it), [])
 
 if __name__ == "__main__":
     unittest.main()
diff --git a/Misc/NEWS.d/next/Core and Builtins/2024-07-08-10-31-08.gh-issue-121012.M5hHk-.rst b/Misc/NEWS.d/next/Core and Builtins/2024-07-08-10-31-08.gh-issue-121012.M5hHk-.rst
new file mode 100644
index 00000000000..7b04eb68b03
--- /dev/null
+++ b/Misc/NEWS.d/next/Core and Builtins/2024-07-08-10-31-08.gh-issue-121012.M5hHk-.rst	
@@ -0,0 +1,2 @@
+Tier 2 execution now ensures that list iterators remain exhausted, once they
+become exhausted.
diff --git a/Python/bytecodes.c b/Python/bytecodes.c
index 76587a4f0dc..84241c64ffa 100644
--- a/Python/bytecodes.c
+++ b/Python/bytecodes.c
@@ -2967,7 +2967,10 @@ dummy_func(
             assert(Py_TYPE(iter_o) == &PyListIter_Type);
             PyListObject *seq = it->it_seq;
             EXIT_IF(seq == NULL);
-            EXIT_IF((size_t)it->it_index >= (size_t)PyList_GET_SIZE(seq));
+            if ((size_t)it->it_index >= (size_t)PyList_GET_SIZE(seq)) {
+                it->it_index = -1;
+                EXIT_IF(1);
+            }
         }
 
         op(_ITER_NEXT_LIST, (iter -- iter, next)) {
diff --git a/Python/executor_cases.c.h b/Python/executor_cases.c.h
index 3b999465aac..8f6bc75b528 100644
--- a/Python/executor_cases.c.h
+++ b/Python/executor_cases.c.h
@@ -3055,8 +3055,11 @@
                 JUMP_TO_JUMP_TARGET();
             }
             if ((size_t)it->it_index >= (size_t)PyList_GET_SIZE(seq)) {
-                UOP_STAT_INC(uopcode, miss);
-                JUMP_TO_JUMP_TARGET();
+                it->it_index = -1;
+                if (1) {
+                    UOP_STAT_INC(uopcode, miss);
+                    JUMP_TO_JUMP_TARGET();
+                }
             }
             break;
         }