diff --git a/changelog.d/9725.bugfix b/changelog.d/9725.bugfix
new file mode 100644
index 0000000000..71283685c8
--- /dev/null
+++ b/changelog.d/9725.bugfix
@@ -0,0 +1 @@
+Fix longstanding bug which caused `duplicate key value violates unique constraint "remote_media_cache_thumbnails_media_origin_media_id_thumbna_key"` errors.
diff --git a/synapse/storage/databases/main/media_repository.py b/synapse/storage/databases/main/media_repository.py
index 4f3d192562..b7820ac7ff 100644
--- a/synapse/storage/databases/main/media_repository.py
+++ b/synapse/storage/databases/main/media_repository.py
@@ -22,6 +22,9 @@ from synapse.storage.database import DatabasePool
 BG_UPDATE_REMOVE_MEDIA_REPO_INDEX_WITHOUT_METHOD = (
     "media_repository_drop_index_wo_method"
 )
+BG_UPDATE_REMOVE_MEDIA_REPO_INDEX_WITHOUT_METHOD_2 = (
+    "media_repository_drop_index_wo_method_2"
+)
 
 
 class MediaSortOrder(Enum):
@@ -85,23 +88,35 @@ class MediaRepositoryBackgroundUpdateStore(SQLBaseStore):
             unique=True,
         )
 
+        # the original impl of _drop_media_index_without_method was broken (see
+        # https://github.com/matrix-org/synapse/issues/8649), so we replace the original
+        # impl with a no-op and run the fixed migration as
+        # media_repository_drop_index_wo_method_2.
+        self.db_pool.updates.register_noop_background_update(
+            BG_UPDATE_REMOVE_MEDIA_REPO_INDEX_WITHOUT_METHOD
+        )
         self.db_pool.updates.register_background_update_handler(
-            BG_UPDATE_REMOVE_MEDIA_REPO_INDEX_WITHOUT_METHOD,
+            BG_UPDATE_REMOVE_MEDIA_REPO_INDEX_WITHOUT_METHOD_2,
             self._drop_media_index_without_method,
         )
 
     async def _drop_media_index_without_method(self, progress, batch_size):
+        """background update handler which removes the old constraints.
+
+        Note that this is only run on postgres.
+        """
+
         def f(txn):
             txn.execute(
                 "ALTER TABLE local_media_repository_thumbnails DROP CONSTRAINT IF EXISTS local_media_repository_thumbn_media_id_thumbnail_width_thum_key"
             )
             txn.execute(
-                "ALTER TABLE remote_media_cache_thumbnails DROP CONSTRAINT IF EXISTS remote_media_repository_thumbn_media_id_thumbnail_width_thum_key"
+                "ALTER TABLE remote_media_cache_thumbnails DROP CONSTRAINT IF EXISTS remote_media_cache_thumbnails_media_origin_media_id_thumbna_key"
             )
 
         await self.db_pool.runInteraction("drop_media_indices_without_method", f)
         await self.db_pool.updates._end_background_update(
-            BG_UPDATE_REMOVE_MEDIA_REPO_INDEX_WITHOUT_METHOD
+            BG_UPDATE_REMOVE_MEDIA_REPO_INDEX_WITHOUT_METHOD_2
         )
         return 1
 
diff --git a/synapse/storage/databases/main/schema/delta/59/11drop_thumbnail_constraint.sql.postgres b/synapse/storage/databases/main/schema/delta/59/11drop_thumbnail_constraint.sql.postgres
new file mode 100644
index 0000000000..54c1bca3b1
--- /dev/null
+++ b/synapse/storage/databases/main/schema/delta/59/11drop_thumbnail_constraint.sql.postgres
@@ -0,0 +1,22 @@
+/* Copyright 2021 The Matrix.org Foundation C.I.C
+ *
+ * Licensed under the Apache License, Version 2.0 (the "License");
+ * you may not use this file except in compliance with the License.
+ * You may obtain a copy of the License at
+ *
+ *    http://www.apache.org/licenses/LICENSE-2.0
+ *
+ * Unless required by applicable law or agreed to in writing, software
+ * distributed under the License is distributed on an "AS IS" BASIS,
+ * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+ * See the License for the specific language governing permissions and
+ * limitations under the License.
+ */
+
+-- drop old constraints on remote_media_cache_thumbnails
+--
+-- This was originally part of 57.07, but it was done wrong, per
+-- https://github.com/matrix-org/synapse/issues/8649, so we do it again.
+INSERT INTO background_updates (ordering, update_name, progress_json, depends_on) VALUES
+  (5911, 'media_repository_drop_index_wo_method_2', '{}', 'remote_media_repository_thumbnails_method_idx');
+