diff --git a/doc/source/whatsnew/v2.0.0.rst b/doc/source/whatsnew/v2.0.0.rst
index e2705b353858b..8896799ffa613 100644
--- a/doc/source/whatsnew/v2.0.0.rst
+++ b/doc/source/whatsnew/v2.0.0.rst
@@ -1276,6 +1276,7 @@ Indexing
 - Bug in :meth:`DataFrame.sort_values` where ``None`` was not returned when ``by`` is empty list and ``inplace=True`` (:issue:`50643`)
 - Bug in :meth:`DataFrame.loc` coercing dtypes when setting values with a list indexer (:issue:`49159`)
 - Bug in :meth:`Series.loc` raising error for out of bounds end of slice indexer (:issue:`50161`)
+- Bug in :meth:`DataFrame.loc` raising ``ValueError`` with all ``False`` ``bool`` indexer and empty object (:issue:`51450`)
 - Bug in :meth:`DataFrame.loc` raising ``ValueError`` with ``bool`` indexer and :class:`MultiIndex` (:issue:`47687`)
 - Bug in :meth:`DataFrame.loc` raising ``IndexError`` when setting values for a pyarrow-backed column with a non-scalar indexer (:issue:`50085`)
 - Bug in :meth:`DataFrame.__getitem__`, :meth:`Series.__getitem__`, :meth:`DataFrame.__setitem__` and :meth:`Series.__setitem__`
diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index c1435ebbe39ef..4c5bc659897d1 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -69,7 +69,6 @@
 )
 from pandas.core.indexers import (
     check_array_indexer,
-    is_empty_indexer,
     is_list_like_indexer,
     is_scalar_indexer,
     length_of_indexer,
@@ -755,14 +754,8 @@ def _maybe_mask_setitem_value(self, indexer, value):
                     if ndim == 1:
                         # We implicitly broadcast, though numpy does not, see
                         # github.com/pandas-dev/pandas/pull/45501#discussion_r789071825
-                        if len(newkey) == 0:
-                            # FIXME: kludge for
-                            #  test_setitem_loc_only_false_indexer_dtype_changed
-                            #  TODO(GH#45333): may be fixed when deprecation is enforced
-                            value = value.iloc[:0]
-                        else:
-                            # test_loc_setitem_ndframe_values_alignment
-                            value = self.obj.iloc._align_series(indexer, value)
+                        # test_loc_setitem_ndframe_values_alignment
+                        value = self.obj.iloc._align_series(indexer, value)
                         indexer = (newkey, icols)
 
                     elif ndim == 2 and value.shape[1] == 1:
@@ -2239,9 +2232,6 @@ def ravel(i):
             # we have a frame, with multiple indexers on both axes; and a
             # series, so need to broadcast (see GH5206)
             if sum_aligners == self.ndim and all(is_sequence(_) for _ in indexer):
-                # TODO: This is hacky, align Series and DataFrame behavior GH#45778
-                if obj.ndim == 2 and is_empty_indexer(indexer[0]):
-                    return ser._values.copy()
                 ser_values = ser.reindex(obj.axes[0][indexer[0]], copy=True)._values
 
                 # single indexer
diff --git a/pandas/tests/indexing/test_loc.py b/pandas/tests/indexing/test_loc.py
index 44c0b654db268..bbea179843f3a 100644
--- a/pandas/tests/indexing/test_loc.py
+++ b/pandas/tests/indexing/test_loc.py
@@ -2599,6 +2599,20 @@ def test_loc_setitem_ndframe_values_alignment(self, using_copy_on_write):
         else:
             tm.assert_frame_equal(df, expected)
 
+    def test_loc_indexer_empty_broadcast(self):
+        # GH#51450
+        df = DataFrame({"a": [], "b": []}, dtype=object)
+        expected = df.copy()
+        df.loc[np.array([], dtype=np.bool_), ["a"]] = df["a"]
+        tm.assert_frame_equal(df, expected)
+
+    def test_loc_indexer_all_false_broadcast(self):
+        # GH#51450
+        df = DataFrame({"a": ["x"], "b": ["y"]}, dtype=object)
+        expected = df.copy()
+        df.loc[np.array([False], dtype=np.bool_), ["a"]] = df["b"]
+        tm.assert_frame_equal(df, expected)
+
 
 class TestLocListlike:
     @pytest.mark.parametrize("box", [lambda x: x, np.asarray, list])