diff --git a/doc/source/whatsnew/v0.23.5.txt b/doc/source/whatsnew/v0.23.5.txt
index ee0ee4259f86d..916a246355b5f 100644
--- a/doc/source/whatsnew/v0.23.5.txt
+++ b/doc/source/whatsnew/v0.23.5.txt
@@ -20,6 +20,9 @@ and bug fixes. We recommend that all users upgrade to this version.
 Fixed Regressions
 ~~~~~~~~~~~~~~~~~
 
+- Constructing a DataFrame with an index argument that wasn't already an
+  instance of :class:`~pandas.core.Index` was broken in `4efb39f
+  <https://github.com/pandas-dev/pandas/commit/4efb39f01f5880122fa38d91e12d217ef70fad9e>`_ (:issue:`22227`).
 -
 -
 
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 2a40dd28a6fd7..54d4006c78de4 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -7354,6 +7354,8 @@ def _arrays_to_mgr(arrays, arr_names, index, columns, dtype=None):
     # figure out the index, if necessary
     if index is None:
         index = extract_index(arrays)
+    else:
+        index = ensure_index(index)
 
     # don't force copy because getting jammed in an ndarray anyway
     arrays = _homogenize(arrays, index, dtype)
diff --git a/pandas/tests/frame/test_constructors.py b/pandas/tests/frame/test_constructors.py
index 70dd358248bc4..849e617c47824 100644
--- a/pandas/tests/frame/test_constructors.py
+++ b/pandas/tests/frame/test_constructors.py
@@ -2230,3 +2230,16 @@ def test_frame_timeseries_column(self):
             Timestamp('20130101T10:01:00', tz='US/Eastern'),
             Timestamp('20130101T10:02:00', tz='US/Eastern')]})
         tm.assert_frame_equal(result, expected)
+
+    def test_nested_dict_construction(self):
+        # GH22227
+        columns = ['Nevada', 'Ohio']
+        pop = {'Nevada': {2001: 2.4, 2002: 2.9},
+               'Ohio': {2000: 1.5, 2001: 1.7, 2002: 3.6}}
+        result = pd.DataFrame(pop, index=[2001, 2002, 2003], columns=columns)
+        expected = pd.DataFrame(
+            [(2.4, 1.7), (2.9, 3.6), (np.nan, np.nan)],
+            columns=columns,
+            index=pd.Index([2001, 2002, 2003])
+        )
+        tm.assert_frame_equal(result, expected)