diff --git a/include/pybind11/operators.h b/include/pybind11/operators.h
index a0c3b78d6..16a88ae17 100644
--- a/include/pybind11/operators.h
+++ b/include/pybind11/operators.h
@@ -84,6 +84,7 @@ struct op_impl {};
 /// Operator implementation generator
 template <op_id id, op_type ot, typename L, typename R>
 struct op_ {
+    static constexpr bool op_enable_if_hook = true;
     template <typename Class, typename... Extra>
     void execute(Class &cl, const Extra &...extra) const {
         using Base = typename Class::type;
diff --git a/include/pybind11/pybind11.h b/include/pybind11/pybind11.h
index 3f6e27b75..fb4b7578d 100644
--- a/include/pybind11/pybind11.h
+++ b/include/pybind11/pybind11.h
@@ -1578,34 +1578,17 @@ public:
         return *this;
     }
 
-// Nvidia's NVCC is broken between 11.4.0 and 11.8.0
-//   https://github.com/pybind/pybind11/issues/4193
-#if defined(__CUDACC__) && (__CUDACC_VER_MAJOR__ == 11) && (__CUDACC_VER_MINOR__ >= 4)            \
-    && (__CUDACC_VER_MINOR__ <= 8)
-    template <typename T, typename... Extra>
+    template <typename T, typename... Extra, detail::enable_if_t<T::op_enable_if_hook, int> = 0>
     class_ &def(const T &op, const Extra &...extra) {
         op.execute(*this, extra...);
         return *this;
     }
 
-    template <typename T, typename... Extra>
+    template <typename T, typename... Extra, detail::enable_if_t<T::op_enable_if_hook, int> = 0>
     class_ &def_cast(const T &op, const Extra &...extra) {
         op.execute_cast(*this, extra...);
         return *this;
     }
-#else
-    template <detail::op_id id, detail::op_type ot, typename L, typename R, typename... Extra>
-    class_ &def(const detail::op_<id, ot, L, R> &op, const Extra &...extra) {
-        op.execute(*this, extra...);
-        return *this;
-    }
-
-    template <detail::op_id id, detail::op_type ot, typename L, typename R, typename... Extra>
-    class_ &def_cast(const detail::op_<id, ot, L, R> &op, const Extra &...extra) {
-        op.execute_cast(*this, extra...);
-        return *this;
-    }
-#endif
 
     template <typename... Args, typename... Extra>
     class_ &def(const detail::initimpl::constructor<Args...> &init, const Extra &...extra) {
diff --git a/tests/test_class.cpp b/tests/test_class.cpp
index c8b8071dc..18c8d358b 100644
--- a/tests/test_class.cpp
+++ b/tests/test_class.cpp
@@ -36,6 +36,26 @@ struct NoBraceInitialization {
     std::vector<int> vec;
 };
 
+namespace test_class {
+namespace pr4220_tripped_over_this { // PR #4227
+
+template <int>
+struct SoEmpty {};
+
+template <typename T>
+std::string get_msg(const T &) {
+    return "This is really only meant to exercise successful compilation.";
+}
+
+using Empty0 = SoEmpty<0x0>;
+
+void bind_empty0(py::module_ &m) {
+    py::class_<Empty0>(m, "Empty0").def(py::init<>()).def("get_msg", get_msg<Empty0>);
+}
+
+} // namespace pr4220_tripped_over_this
+} // namespace test_class
+
 TEST_SUBMODULE(class_, m) {
     // test_instance
     struct NoConstructor {
@@ -517,6 +537,8 @@ TEST_SUBMODULE(class_, m) {
         py::class_<OtherDuplicateNested>(gt, "OtherDuplicateNested");
         py::class_<OtherDuplicateNested>(gt, "YetAnotherDuplicateNested");
     });
+
+    test_class::pr4220_tripped_over_this::bind_empty0(m);
 }
 
 template <int N>
diff --git a/tests/test_class.py b/tests/test_class.py
index ff9196f0f..47ba450fc 100644
--- a/tests/test_class.py
+++ b/tests/test_class.py
@@ -469,3 +469,10 @@ def test_register_duplicate_class():
         m.register_duplicate_nested_class_type(ClassScope)
     expected = 'generic_type: type "YetAnotherDuplicateNested" is already registered!'
     assert str(exc_info.value) == expected
+
+
+def test_pr4220_tripped_over_this():
+    assert (
+        m.Empty0().get_msg()
+        == "This is really only meant to exercise successful compilation."
+    )