diff --git a/mypy/typeanal.py b/mypy/typeanal.py
index f7b584eadae8..e0e8eca26587 100644
--- a/mypy/typeanal.py
+++ b/mypy/typeanal.py
@@ -162,6 +162,8 @@ def __init__(self,
         self.is_typeshed_stub = is_typeshed_stub
         # Names of type aliases encountered while analysing a type will be collected here.
         self.aliases_used: Set[str] = set()
+        # Is needed for `TypeGuard` analysis:
+        self.is_return_type = False
 
     def visit_unbound_type(self, t: UnboundType, defining_literal: bool = False) -> Type:
         typ = self.visit_unbound_type_nonoptional(t, defining_literal)
@@ -562,7 +564,7 @@ def visit_callable_type(self, t: CallableType, nested: bool = True) -> Type:
                 variables = t.variables
             else:
                 variables = self.bind_function_type_variables(t, t)
-            special = self.anal_type_guard(t.ret_type)
+            special = self.anal_type_guard(t.ret_type, explicit=True)
             arg_kinds = t.arg_kinds
             if len(arg_kinds) >= 2 and arg_kinds[-2] == ARG_STAR and arg_kinds[-1] == ARG_STAR2:
                 arg_types = self.anal_array(t.arg_types[:-2], nested=nested) + [
@@ -571,30 +573,35 @@ def visit_callable_type(self, t: CallableType, nested: bool = True) -> Type:
                 ]
             else:
                 arg_types = self.anal_array(t.arg_types, nested=nested)
-            ret = t.copy_modified(arg_types=arg_types,
-                                  ret_type=self.anal_type(t.ret_type, nested=nested),
-                                  # If the fallback isn't filled in yet,
-                                  # its type will be the falsey FakeInfo
-                                  fallback=(t.fallback if t.fallback.type
-                                            else self.named_type('builtins.function')),
-                                  variables=self.anal_var_defs(variables),
-                                  type_guard=special,
-                                  )
+            ret = t.copy_modified(
+                arg_types=arg_types,
+                ret_type=self.anal_type(t.ret_type, nested=nested, is_return_type=True),
+                # If the fallback isn't filled in yet,
+                # its type will be the falsey FakeInfo
+                fallback=(t.fallback if t.fallback.type
+                        else self.named_type('builtins.function')),
+                variables=self.anal_var_defs(variables),
+                type_guard=special,
+            )
         return ret
 
-    def anal_type_guard(self, t: Type) -> Optional[Type]:
+    def anal_type_guard(self, t: Type, *, explicit: bool = False) -> Optional[Type]:
         if isinstance(t, UnboundType):
             sym = self.lookup_qualified(t.name, t)
             if sym is not None and sym.node is not None:
-                return self.anal_type_guard_arg(t, sym.node.fullname)
+                return self.anal_type_guard_arg(t, sym.node.fullname, explicit=explicit)
         # TODO: What if it's an Instance? Then use t.type.fullname?
         return None
 
-    def anal_type_guard_arg(self, t: UnboundType, fullname: str) -> Optional[Type]:
+    def anal_type_guard_arg(
+        self, t: UnboundType, fullname: str, *, explicit: bool = False,
+    ) -> Optional[Type]:
         if fullname in ('typing_extensions.TypeGuard', 'typing.TypeGuard'):
             if len(t.args) != 1:
                 self.fail("TypeGuard must have exactly one type argument", t)
                 return AnyType(TypeOfAny.from_error)
+            if not (explicit or self.is_return_type):
+                self.fail('TypeGuard must only be used as a return type', t)
             return self.anal_type(t.args[0])
         return None
 
@@ -1011,17 +1018,26 @@ def anal_array(self,
             res.append(self.anal_type(t, nested, allow_param_spec=allow_param_spec))
         return res
 
-    def anal_type(self, t: Type, nested: bool = True, *, allow_param_spec: bool = False) -> Type:
+    def anal_type(
+        self,
+        t: Type,
+        nested: bool = True,
+        *,
+        allow_param_spec: bool = False,
+        is_return_type: bool = False,
+    ) -> Type:
         if nested:
             self.nesting_level += 1
         old_allow_required = self.allow_required
         self.allow_required = False
+        self.is_return_type = is_return_type
         try:
             analyzed = t.accept(self)
         finally:
             if nested:
                 self.nesting_level -= 1
             self.allow_required = old_allow_required
+            self.is_return_type = False
         if (not allow_param_spec
                 and isinstance(analyzed, ParamSpecType)
                 and analyzed.flavor == ParamSpecFlavor.BARE):
diff --git a/test-data/unit/check-typeguard.test b/test-data/unit/check-typeguard.test
index 32fe5e750989..40e7802c26c8 100644
--- a/test-data/unit/check-typeguard.test
+++ b/test-data/unit/check-typeguard.test
@@ -55,13 +55,18 @@ def main(a: object, b: object) -> None:
 [builtins fixtures/tuple.pyi]
 
 [case testTypeGuardIsBool]
+from typing import List
 from typing_extensions import TypeGuard
-def f(a: TypeGuard[int]) -> None: pass
+def f(a: TypeGuard[int]) -> None:  # E: TypeGuard must only be used as a return type
+    pass
 reveal_type(f)  # N: Revealed type is "def (a: builtins.bool)"
-a: TypeGuard[int]
+def f1() -> List[TypeGuard[int]]:  # E: TypeGuard must only be used as a return type
+    pass
+reveal_type(f1())  # N: Revealed type is "builtins.list[builtins.bool]"
+a: TypeGuard[int]  # E: TypeGuard must only be used as a return type
 reveal_type(a)  # N: Revealed type is "builtins.bool"
 class C:
-    a: TypeGuard[int]
+    a: TypeGuard[int]  # E: TypeGuard must only be used as a return type
 reveal_type(C().a)  # N: Revealed type is "builtins.bool"
 [builtins fixtures/tuple.pyi]