diff --git a/doc/source/whatsnew/v1.4.2.rst b/doc/source/whatsnew/v1.4.2.rst
index 9ba7461b830da..fdac1c385499a 100644
--- a/doc/source/whatsnew/v1.4.2.rst
+++ b/doc/source/whatsnew/v1.4.2.rst
@@ -14,7 +14,7 @@ including other versions of pandas.
 
 Fixed regressions
 ~~~~~~~~~~~~~~~~~
--
+- Fixed regression in :meth:`DataFrame.drop` and :meth:`Series.drop` when :class:`Index` had extension dtype and duplicates (:issue:`45820`)
 -
 
 .. ---------------------------------------------------------------------------
diff --git a/pandas/core/generic.py b/pandas/core/generic.py
index b329f4fb00ccc..d155ed95ae3eb 100644
--- a/pandas/core/generic.py
+++ b/pandas/core/generic.py
@@ -4342,6 +4342,10 @@ def _drop_axis(
                 if errors == "raise" and labels_missing:
                     raise KeyError(f"{labels} not found in axis")
 
+            if is_extension_array_dtype(mask.dtype):
+                # GH#45860
+                mask = mask.to_numpy(dtype=bool)
+
             indexer = mask.nonzero()[0]
             new_axis = axis.take(indexer)
 
diff --git a/pandas/tests/frame/methods/test_drop.py b/pandas/tests/frame/methods/test_drop.py
index 4f8ea6eda1b5f..50b60f9e06ef1 100644
--- a/pandas/tests/frame/methods/test_drop.py
+++ b/pandas/tests/frame/methods/test_drop.py
@@ -537,3 +537,15 @@ def test_drop_level_missing_label_multiindex(self):
         df = DataFrame(index=MultiIndex.from_product([range(3), range(3)]))
         with pytest.raises(KeyError, match="labels \\[5\\] not found in level"):
             df.drop(5, level=0)
+
+    @pytest.mark.parametrize("idx, level", [(["a", "b"], 0), (["a"], None)])
+    def test_drop_index_ea_dtype(self, any_numeric_ea_dtype, idx, level):
+        # GH#45860
+        df = DataFrame(
+            {"a": [1, 2, 2, pd.NA], "b": 100}, dtype=any_numeric_ea_dtype
+        ).set_index(idx)
+        result = df.drop(Index([2, pd.NA]), level=level)
+        expected = DataFrame(
+            {"a": [1], "b": 100}, dtype=any_numeric_ea_dtype
+        ).set_index(idx)
+        tm.assert_frame_equal(result, expected)
diff --git a/pandas/tests/series/methods/test_drop.py b/pandas/tests/series/methods/test_drop.py
index a625e890393a6..c960c281b2b95 100644
--- a/pandas/tests/series/methods/test_drop.py
+++ b/pandas/tests/series/methods/test_drop.py
@@ -1,6 +1,9 @@
 import pytest
 
-from pandas import Series
+from pandas import (
+    Index,
+    Series,
+)
 import pandas._testing as tm
 
 
@@ -98,3 +101,12 @@ def test_drop_pos_args_deprecation():
         result = ser.drop(1, 0)
     expected = Series([1, 3], index=[0, 2])
     tm.assert_series_equal(result, expected)
+
+
+def test_drop_index_ea_dtype(any_numeric_ea_dtype):
+    # GH#45860
+    df = Series(100, index=Index([1, 2, 2], dtype=any_numeric_ea_dtype))
+    idx = Index([df.index[1]])
+    result = df.drop(idx)
+    expected = Series(100, index=Index([1], dtype=any_numeric_ea_dtype))
+    tm.assert_series_equal(result, expected)