diff --git a/doc/source/whatsnew/v1.2.0.rst b/doc/source/whatsnew/v1.2.0.rst
index 28f7df98cb86b..30d6095639a00 100644
--- a/doc/source/whatsnew/v1.2.0.rst
+++ b/doc/source/whatsnew/v1.2.0.rst
@@ -584,6 +584,7 @@ Indexing
 - Bug in :meth:`DataFrame.loc` returned requested key plus missing values when ``loc`` was applied to single level from :class:`MultiIndex` (:issue:`27104`)
 - Bug in indexing on a :class:`Series` or :class:`DataFrame` with a :class:`CategoricalIndex` using a listlike indexer containing NA values (:issue:`37722`)
 - Bug in :meth:`DataFrame.xs` ignored ``droplevel=False`` for columns (:issue:`19056`)
+- Bug in :meth:`DataFrame.reindex` raising ``IndexingError`` wrongly for empty :class:`DataFrame` with ``tolerance`` not None or ``method="nearest"`` (:issue:`27315`)
 
 Missing
 ^^^^^^^
diff --git a/pandas/core/indexes/base.py b/pandas/core/indexes/base.py
index cb5641a74e60b..30b582f854b57 100644
--- a/pandas/core/indexes/base.py
+++ b/pandas/core/indexes/base.py
@@ -3163,7 +3163,7 @@ def _get_fill_indexer(
             indexer = engine_method(target_values, limit)
         else:
             indexer = self._get_fill_indexer_searchsorted(target, method, limit)
-        if tolerance is not None:
+        if tolerance is not None and len(self):
             indexer = self._filter_indexer_tolerance(target_values, indexer, tolerance)
         return indexer
 
@@ -3208,6 +3208,9 @@ def _get_nearest_indexer(self, target: "Index", limit, tolerance) -> np.ndarray:
         values that can be subtracted from each other (e.g., not strings or
         tuples).
         """
+        if not len(self):
+            return self._get_fill_indexer(target, "pad")
+
         left_indexer = self.get_indexer(target, "pad", limit=limit)
         right_indexer = self.get_indexer(target, "backfill", limit=limit)
 
diff --git a/pandas/tests/frame/methods/test_reindex.py b/pandas/tests/frame/methods/test_reindex.py
index 113a80f1c5c4e..3e4e16955b44a 100644
--- a/pandas/tests/frame/methods/test_reindex.py
+++ b/pandas/tests/frame/methods/test_reindex.py
@@ -1,4 +1,4 @@
-from datetime import datetime
+from datetime import datetime, timedelta
 import inspect
 from itertools import permutations
 
@@ -874,3 +874,20 @@ def test_reindex_multiindex_ffill_added_rows(self):
         result = df.reindex(mi2, axis=0, method="ffill")
         expected = DataFrame([[0, 7], [3, 4], [3, 4]], index=mi2, columns=["x", "y"])
         tm.assert_frame_equal(result, expected)
+
+    @pytest.mark.parametrize(
+        "kwargs",
+        [
+            {"method": "pad", "tolerance": timedelta(seconds=9)},
+            {"method": "backfill", "tolerance": timedelta(seconds=9)},
+            {"method": "nearest"},
+            {"method": None},
+        ],
+    )
+    def test_reindex_empty_frame(self, kwargs):
+        # GH#27315
+        idx = date_range(start="2020", freq="30s", periods=3)
+        df = DataFrame([], index=Index([], name="time"), columns=["a"])
+        result = df.reindex(idx, **kwargs)
+        expected = DataFrame({"a": [pd.NA] * 3}, index=idx)
+        tm.assert_frame_equal(result, expected)