diff --git a/Lib/re/_parser.py b/Lib/re/_parser.py
index 22d10ab6e31..d00b7e67d55 100644
--- a/Lib/re/_parser.py
+++ b/Lib/re/_parser.py
@@ -773,8 +773,10 @@ def _parse(source, state, verbose, nested, first=False):
                                            source.tell() - start)
                     if char == "=":
                         subpatternappend((ASSERT, (dir, p)))
-                    else:
+                    elif p:
                         subpatternappend((ASSERT_NOT, (dir, p)))
+                    else:
+                        subpatternappend((FAILURE, ()))
                     continue
 
                 elif char == "(":
diff --git a/Lib/test/test_re.py b/Lib/test/test_re.py
index a6f5af17d7d..a565cbe1a8d 100644
--- a/Lib/test/test_re.py
+++ b/Lib/test/test_re.py
@@ -2362,6 +2362,9 @@ class ReTests(unittest.TestCase):
                 p.terminate()
                 p.join()
 
+    def test_fail(self):
+        self.assertEqual(re.search(r'12(?!)|3', '123')[0], '3')
+
 
 def get_debug_out(pat):
     with captured_stdout() as out:
diff --git a/Misc/NEWS.d/next/Library/2023-07-09-13-10-54.gh-issue-106566.NN35-U.rst b/Misc/NEWS.d/next/Library/2023-07-09-13-10-54.gh-issue-106566.NN35-U.rst
new file mode 100644
index 00000000000..3b88dc79183
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2023-07-09-13-10-54.gh-issue-106566.NN35-U.rst
@@ -0,0 +1 @@
+Optimize ``(?!)`` (pattern which alwais fails) in regular expressions.