diff --git a/CMake/ITKModuleTest.cmake b/CMake/ITKModuleTest.cmake
index 9e957fe9a6c..7e8b98e1a64 100644
--- a/CMake/ITKModuleTest.cmake
+++ b/CMake/ITKModuleTest.cmake
@@ -337,3 +337,79 @@ function(itk_memcheck_ignore)
         ${ARGN}
   )
 endfunction()
+
+#-----------------------------------------------------------------------------
+# Option to automatically remove large test output files after completion.
+# BigIO write-read tests can produce multi-gigabyte temporary files
+# that exhaust disk space on CI runners and local builds.
+option(
+  ITK_REMOVE_TEST_FILES_ON_SUCCESS
+  "Remove large test output files after test completion. Set OFF to retain files for debugging."
+  ON
+)
+mark_as_advanced(ITK_REMOVE_TEST_FILES_ON_SUCCESS)
+
+#-----------------------------------------------------------------------------
+# itk_add_file_test_cleanup(<test_name> <output_file> [<output_file2> ...])
+#
+# Adds a cleanup test that removes the given output files after <test_name>
+# completes.  Uses CTest fixtures: the main test is declared FIXTURES_SETUP
+# and the companion <test_name>_cleanup test is declared FIXTURES_CLEANUP.
+#
+# NOTE: Per CMake documentation, FIXTURES_CLEANUP tests execute
+# unconditionally after their fixture — they run regardless of whether the
+# SETUP test passed, failed, or was skipped.  To retain output files for
+# debugging after a failure, set ITK_REMOVE_TEST_FILES_ON_SUCCESS=OFF.
+#
+# NOTE: In a full unfiltered run all tests (including *_cleanup variants)
+# are in the active set and fixture ordering is respected.  When rerunning
+# a single test with a strict filter (e.g. ctest -R "^<test_name>$"),
+# the *_cleanup test does not match; omit the anchors (ctest -R <test_name>)
+# so both the main test and its cleanup are selected.
+#
+# When ITK_REMOVE_TEST_FILES_ON_SUCCESS is OFF, no cleanup test is added
+# and the output files are retained for manual inspection.
+#
+function(itk_add_file_test_cleanup TEST_NAME)
+  if(NOT ITK_REMOVE_TEST_FILES_ON_SUCCESS)
+    return()
+  endif()
+
+  set(FIXTURE_NAME "Cleanup_${TEST_NAME}")
+
+  # Make the main test the SETUP of this fixture
+  set_tests_properties(
+    ${TEST_NAME}
+    PROPERTIES
+      FIXTURES_SETUP
+        ${FIXTURE_NAME}
+  )
+
+  # Build the removal command for all output files
+  set(RM_ARGS "")
+  foreach(OUTPUT_FILE ${ARGN})
+    # For .mhd files, also remove the companion .raw/.zraw
+    get_filename_component(EXT "${OUTPUT_FILE}" LAST_EXT)
+    get_filename_component(BASE_NAME "${OUTPUT_FILE}" NAME_WLE)
+    get_filename_component(DIR "${OUTPUT_FILE}" DIRECTORY)
+    list(APPEND RM_ARGS "${OUTPUT_FILE}")
+    if("${EXT}" STREQUAL ".mhd")
+      list(APPEND RM_ARGS "${DIR}/${BASE_NAME}.raw")
+      list(APPEND RM_ARGS "${DIR}/${BASE_NAME}.zraw")
+    endif()
+  endforeach()
+
+  add_test(
+    NAME ${TEST_NAME}_cleanup
+    COMMAND
+      ${CMAKE_COMMAND} -E rm -f ${RM_ARGS}
+  )
+  set_tests_properties(
+    ${TEST_NAME}_cleanup
+    PROPERTIES
+      FIXTURES_CLEANUP
+        ${FIXTURE_NAME}
+      LABELS
+        "CLEANUP"
+  )
+endfunction()
diff --git a/Modules/IO/ImageBase/test/CMakeLists.txt b/Modules/IO/ImageBase/test/CMakeLists.txt
index 9a990b499de..bb9d2867113 100644
--- a/Modules/IO/ImageBase/test/CMakeLists.txt
+++ b/Modules/IO/ImageBase/test/CMakeLists.txt
@@ -52,12 +52,6 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 16)
       ${ITK_TEST_OUTPUT_DIR}/itkLargeImageWriteConvertReadTest.mha
       30000L
   )
-  set_tests_properties(
-    itkLargeImageWriteConvertReadTest
-    PROPERTIES
-      RESOURCE_LOCK
-        MEMORY_SIZE
-  )
 
   itk_add_test(
     NAME itkLargeImageWriteReadTest_2D
@@ -67,12 +61,6 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 16)
       ${ITK_TEST_OUTPUT_DIR}/itkLargeImageWriteReadTest_2D.mha
       30000L
   )
-  set_tests_properties(
-    itkLargeImageWriteReadTest_2D
-    PROPERTIES
-      RESOURCE_LOCK
-        MEMORY_SIZE
-  )
 
   itk_add_test(
     NAME itkLargeImageWriteReadTest_3D
@@ -83,11 +71,28 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 16)
       30000L
       4L
   )
+
+  # BigIO tests produce multi-gigabyte files; MEMORY_SIZE lock serializes them
   set_tests_properties(
+    itkLargeImageWriteConvertReadTest
+    itkLargeImageWriteReadTest_2D
     itkLargeImageWriteReadTest_3D
     PROPERTIES
       RESOURCE_LOCK
         MEMORY_SIZE
+      LABELS
+        "BigIO;RUNS_LONG"
+  )
+
+  # Clean up BigIO output files after completion
+  itk_add_file_test_cleanup(
+    itkLargeImageWriteConvertReadTest ${ITK_TEST_OUTPUT_DIR}/itkLargeImageWriteConvertReadTest.mha
+  )
+  itk_add_file_test_cleanup(
+    itkLargeImageWriteReadTest_2D ${ITK_TEST_OUTPUT_DIR}/itkLargeImageWriteReadTest_2D.mha
+  )
+  itk_add_file_test_cleanup(
+    itkLargeImageWriteReadTest_3D ${ITK_TEST_OUTPUT_DIR}/itkLargeImageWriteReadTest_3D.mha
   )
 endif()
 
diff --git a/Modules/IO/Meta/test/CMakeLists.txt b/Modules/IO/Meta/test/CMakeLists.txt
index 84d87ef5e43..fbab393885e 100644
--- a/Modules/IO/Meta/test/CMakeLists.txt
+++ b/Modules/IO/Meta/test/CMakeLists.txt
@@ -482,7 +482,7 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 5)
       50000L
   )
 
-  # Due to the large memory requirements this tests must be run one by one
+  # Due to the large memory requirements these tests must be run one by one
   set_tests_properties(
     itkLargeMetaImageWriteReadTest1
     itkLargeMetaImageWriteReadTest2
@@ -519,6 +519,10 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 5)
       LABELS
         RUNS_LONG
   )
+  # Clean up BigIO output files after completion
+  itk_add_file_test_cleanup(itkLargeMetaImageWriteReadTest1 ${ITK_TEST_OUTPUT_DIR}/LargeImage01.mhd)
+  itk_add_file_test_cleanup(itkLargeMetaImageWriteReadTest2 ${ITK_TEST_OUTPUT_DIR}/LargeImage02.mhd)
+  itk_add_file_test_cleanup(itkLargeMetaImageWriteReadTest3 ${ITK_TEST_OUTPUT_DIR}/LargeImage03.mhd)
 endif()
 
 if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 12)
@@ -532,7 +536,7 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 12)
       70000L
   )
 
-  # Due to the large memory requirements this tests must be run one by one
+  # Due to the large memory requirements this test must be run serially
   set_tests_properties(
     itkLargeMetaImageWriteReadTest4
     PROPERTIES
@@ -542,6 +546,8 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 12)
         MEMORY_SIZE
       COST
         30
+      RUN_SERIAL
+        True
   )
   set_property(
     TEST
@@ -551,12 +557,5 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 12)
       LABELS
         RUNS_LONG
   )
-  set_property(
-    TEST
-      itkLargeMetaImageWriteReadTest4
-    APPEND
-    PROPERTY
-      RUN_SERIAL
-        True
-  )
+  itk_add_file_test_cleanup(itkLargeMetaImageWriteReadTest4 ${ITK_TEST_OUTPUT_DIR}/LargeImage04.mhd)
 endif()
diff --git a/Modules/IO/TIFF/test/CMakeLists.txt b/Modules/IO/TIFF/test/CMakeLists.txt
index 1dd906b9508..a3b0766e5f6 100644
--- a/Modules/IO/TIFF/test/CMakeLists.txt
+++ b/Modules/IO/TIFF/test/CMakeLists.txt
@@ -486,7 +486,7 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 5)
       50000L
   )
 
-  # Due to the large memory requirements this tests must be run one by one
+  # Due to the large memory requirements these tests must be run one by one
   set_tests_properties(
     itkLargeTIFFImageWriteReadTest1
     itkLargeTIFFImageWriteReadTest2
@@ -496,6 +496,8 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 5)
         BigIO
       RESOURCE_LOCK
         MEMORY_SIZE
+      RUN_SERIAL
+        True
   )
   set_property(
     TEST
@@ -505,14 +507,6 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 5)
       LABELS
         RUNS_LONG
   )
-  set_property(
-    TEST
-      itkLargeTIFFImageWriteReadTest1
-    APPEND
-    PROPERTY
-      RUN_SERIAL
-        True
-  )
   set_property(
     TEST
       itkLargeTIFFImageWriteReadTest2
@@ -521,14 +515,6 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 5)
       LABELS
         RUNS_LONG
   )
-  set_property(
-    TEST
-      itkLargeTIFFImageWriteReadTest2
-    APPEND
-    PROPERTY
-      RUN_SERIAL
-        True
-  )
   set_property(
     TEST
       itkLargeTIFFImageWriteReadTest3
@@ -537,14 +523,10 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 5)
       LABELS
         RUNS_LONG
   )
-  set_property(
-    TEST
-      itkLargeTIFFImageWriteReadTest3
-    APPEND
-    PROPERTY
-      RUN_SERIAL
-        True
-  )
+  # Clean up BigIO output files after completion
+  itk_add_file_test_cleanup(itkLargeTIFFImageWriteReadTest1 ${ITK_TEST_OUTPUT_DIR}/LargeImage01.tif)
+  itk_add_file_test_cleanup(itkLargeTIFFImageWriteReadTest2 ${ITK_TEST_OUTPUT_DIR}/LargeImage02.tif)
+  itk_add_file_test_cleanup(itkLargeTIFFImageWriteReadTest3 ${ITK_TEST_OUTPUT_DIR}/LargeImage03.tif)
 endif()
 
 if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 12)
@@ -558,7 +540,7 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 12)
       70000L
   )
 
-  # Due to the large memory requirements this tests must lock the memory size resource
+  # Due to the large memory requirements this test must be run serially
   set_tests_properties(
     itkLargeTIFFImageWriteReadTest4
     PROPERTIES
@@ -568,6 +550,8 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 12)
         MEMORY_SIZE
       COST
         30
+      RUN_SERIAL
+        True
   )
   set_property(
     TEST
@@ -577,14 +561,7 @@ if("${ITK_COMPUTER_MEMORY_SIZE}" GREATER 12)
       LABELS
         RUNS_LONG
   )
-  set_property(
-    TEST
-      itkLargeTIFFImageWriteReadTest4
-    APPEND
-    PROPERTY
-      RUN_SERIAL
-        True
-  )
+  itk_add_file_test_cleanup(itkLargeTIFFImageWriteReadTest4 ${ITK_TEST_OUTPUT_DIR}/LargeImage04.tif)
 endif()
 
 # expand + RGB image