diff --git a/doc/source/whatsnew/v2.1.2.rst b/doc/source/whatsnew/v2.1.2.rst
index 2c9b10160d144..97aeb56924e65 100644
--- a/doc/source/whatsnew/v2.1.2.rst
+++ b/doc/source/whatsnew/v2.1.2.rst
@@ -13,7 +13,7 @@ including other versions of pandas.
 
 Fixed regressions
 ~~~~~~~~~~~~~~~~~
--
+- Fixed bug where PDEP-6 warning about setting an item of an incompatible dtype was being shown when creating a new conditional column (:issue:`55025`)
 -
 
 .. ---------------------------------------------------------------------------
diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index 871e5817fdf0d..572b668842b9d 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -49,7 +49,6 @@
     ABCSeries,
 )
 from pandas.core.dtypes.missing import (
-    infer_fill_value,
     is_valid_na_for_dtype,
     isna,
     na_value_for_dtype,
@@ -1841,8 +1840,12 @@ def _setitem_with_indexer(self, indexer, value, name: str = "iloc"):
                             self.obj[key] = empty_value
 
                         else:
-                            # FIXME: GH#42099#issuecomment-864326014
-                            self.obj[key] = infer_fill_value(value)
+                            # avoid circular import
+                            from pandas.core.series import Series
+
+                            new = Series(index=self.obj.index)
+                            new[key] = value
+                            self.obj[key] = new
 
                         new_indexer = convert_from_missing_indexer_tuple(
                             indexer, self.obj.axes
diff --git a/pandas/tests/frame/indexing/test_indexing.py b/pandas/tests/frame/indexing/test_indexing.py
index b324291bab31e..a2a88a48cc18c 100644
--- a/pandas/tests/frame/indexing/test_indexing.py
+++ b/pandas/tests/frame/indexing/test_indexing.py
@@ -1890,6 +1890,14 @@ def test_setitem_dict_and_set_disallowed_multiindex(self, key):
             df.loc[key] = 1
 
 
+def test_adding_new_conditional_column() -> None:
+    # https://github.com/pandas-dev/pandas/issues/55025
+    df = DataFrame({"x": [1]})
+    df.loc[df["x"] == 1, "y"] = "1"
+    expected = DataFrame({"x": [1], "y": ["1"]})
+    tm.assert_frame_equal(df, expected)
+
+
 class TestSetitemValidation:
     # This is adapted from pandas/tests/arrays/masked/test_indexing.py
     # but checks for warnings instead of errors.