diff --git a/doc/source/whatsnew/v1.4.0.rst b/doc/source/whatsnew/v1.4.0.rst
index 9ead1e4a75d01..461b9b7d3b93c 100644
--- a/doc/source/whatsnew/v1.4.0.rst
+++ b/doc/source/whatsnew/v1.4.0.rst
@@ -213,6 +213,7 @@ Other enhancements
 - :meth:`.GroupBy.mean` now supports `Numba <http://numba.pydata.org/>`_ execution with the ``engine`` keyword (:issue:`43731`)
 - :meth:`Timestamp.isoformat`, now handles the ``timespec`` argument from the base :class:``datetime`` class (:issue:`26131`)
 - :meth:`NaT.to_numpy` ``dtype`` argument is now respected, so ``np.timedelta64`` can be returned (:issue:`44460`)
+- :meth:`DataFrame.compare` now accepts a ``suffixes`` to allow the user to specify the suffixes of both left and right DataFrame which are being compared. This is by default ``self`` and ``other`` (:issue:`44354`)
 -
 
 
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 33df7a9f0ac1f..2967bea982a08 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -7297,12 +7297,14 @@ def compare(
         align_axis: Axis = 1,
         keep_shape: bool = False,
         keep_equal: bool = False,
+        suffixes: Suffixes = ("self", "other"),
     ) -> DataFrame:
         return super().compare(
             other=other,
             align_axis=align_axis,
             keep_shape=keep_shape,
             keep_equal=keep_equal,
+            suffixes=suffixes,
         )
 
     def combine(
diff --git a/pandas/core/generic.py b/pandas/core/generic.py
index 2db8be19b4399..22ebe91aad6da 100644
--- a/pandas/core/generic.py
+++ b/pandas/core/generic.py
@@ -53,6 +53,7 @@
     RandomState,
     Renamer,
     StorageOptions,
+    Suffixes,
     T,
     TimedeltaConvertibleTypes,
     TimestampConvertibleTypes,
@@ -8538,6 +8539,7 @@ def compare(
         align_axis: Axis = 1,
         keep_shape: bool_t = False,
         keep_equal: bool_t = False,
+        suffixes: Suffixes = ("self", "other"),
     ):
         from pandas.core.reshape.concat import concat
 
@@ -8548,7 +8550,6 @@ def compare(
             )
 
         mask = ~((self == other) | (self.isna() & other.isna()))
-        keys = ["self", "other"]
 
         if not keep_equal:
             self = self.where(mask)
@@ -8569,7 +8570,7 @@ def compare(
         else:
             axis = self._get_axis_number(align_axis)
 
-        diff = concat([self, other], axis=axis, keys=keys)
+        diff = concat([self, other], axis=axis, keys=suffixes)
 
         if axis >= self.ndim:
             # No need to reorganize data if stacking on new axis
diff --git a/pandas/tests/frame/methods/test_compare.py b/pandas/tests/frame/methods/test_compare.py
index 468811eba0d39..ad0c924753e62 100644
--- a/pandas/tests/frame/methods/test_compare.py
+++ b/pandas/tests/frame/methods/test_compare.py
@@ -180,3 +180,20 @@ def test_compare_unaligned_objects():
         df1 = pd.DataFrame(np.ones((3, 3)))
         df2 = pd.DataFrame(np.zeros((2, 1)))
         df1.compare(df2)
+
+
+def test_compare_suffixes():
+    # GH
+    df1 = pd.DataFrame(
+        {"col1": ["a", "b", "c"], "col2": [1.0, 2.0, np.nan], "col3": [1.0, 2.0, 3.0]},
+        columns=["col1", "col2", "col3"],
+    )
+    df2 = df1.copy()
+    df2.loc[0, "col1"] = "c"
+    df2.loc[2, "col3"] = 4.0
+
+    suffixes = ["left", "right"]
+    comp = df1.compare(df2, suffixes=suffixes)
+
+    result_suffixes = comp.columns.get_level_values(1).unique()
+    assert result_suffixes.isin(suffixes).all(), "suffixes not equal"