diff --git a/atdna/CMakeLists.txt b/atdna/CMakeLists.txt
index 1388281..e3b4397 100644
--- a/atdna/CMakeLists.txt
+++ b/atdna/CMakeLists.txt
@@ -152,10 +152,16 @@ endif()
 
 # Super handy macro for adding atdna target
 macro(atdna out)
+  # Ninja wants invocations in root binary dir for DEPFILE application
+  file(RELATIVE_PATH out_rel ${CMAKE_BINARY_DIR} "${CMAKE_CURRENT_BINARY_DIR}/${out}")
+
   # Make input files source-relative
   set(ins "")
+  set(ins_impdeps "")
   foreach(arg ${ARGN})
     list(APPEND ins ${CMAKE_CURRENT_SOURCE_DIR}/${arg})
+    list(APPEND ins_impdeps CXX)
+    list(APPEND ins_impdeps ${CMAKE_CURRENT_SOURCE_DIR}/${arg})
   endforeach()
 
   # Get local include directories for atdna
@@ -194,8 +200,22 @@ macro(atdna out)
   endif()
 
   # Make target
-  add_custom_command(OUTPUT ${out} COMMAND $<TARGET_FILE:atdna>
-                     ARGS ${extraargs} -o ${out} ${cdefcli} ${inccli} "-I${ATHENA_INCLUDE_DIR}"
-                     -isystem "${CLANG_INCLUDE_DIR}" ${ins}
-                     DEPENDS ${ins} COMMENT "Generating DNA ${out}")
+  if(${CMAKE_GENERATOR} STREQUAL "Ninja")
+    # Use Ninja's DEPFILE parser in cooperation with atdna
+    add_custom_command(OUTPUT ${out} COMMAND $<TARGET_FILE:atdna>
+                       ARGS ${extraargs} -o ${out_rel} -MD -MT ${out_rel} -MF ${out_rel}.d ${cdefcli} ${inccli}
+                       "-I${ATHENA_INCLUDE_DIR}" -isystem "${CLANG_INCLUDE_DIR}" ${ins}
+                       DEPENDS atdna ${ins} IMPLICIT_DEPENDS ${ins_impdeps}
+                       DEPFILE "${CMAKE_CURRENT_BINARY_DIR}/${out}.d"
+                       WORKING_DIRECTORY ${CMAKE_BINARY_DIR}
+                       COMMENT "Generating DNA ${out_rel}")
+  else()
+    # Use CMake's built-in dependency scanner for makefile targets
+    add_custom_command(OUTPUT ${out} COMMAND $<TARGET_FILE:atdna>
+                       ARGS ${extraargs} -o ${out_rel} ${cdefcli} ${inccli}
+                       "-I${ATHENA_INCLUDE_DIR}" -isystem "${CLANG_INCLUDE_DIR}" ${ins}
+                       DEPENDS atdna ${ins} IMPLICIT_DEPENDS ${ins_impdeps}
+                       WORKING_DIRECTORY ${CMAKE_BINARY_DIR}
+                       COMMENT "Generating DNA ${out_rel}")
+  endif()
 endmacro()
diff --git a/atdna/atdnaConfig.cmake.in b/atdna/atdnaConfig.cmake.in
index d73e53c..5ffad07 100644
--- a/atdna/atdnaConfig.cmake.in
+++ b/atdna/atdnaConfig.cmake.in
@@ -13,10 +13,16 @@ find_package(Athena REQUIRED)
 
 # Super handy macro for adding atdna target
 macro(atdna out)
+  # Ninja wants invocations in root binary dir for DEPFILE application
+  file(RELATIVE_PATH out_rel ${CMAKE_BINARY_DIR} "${CMAKE_CURRENT_BINARY_DIR}/${out}")
+
   # Make input files source-relative
   set(ins "")
+  set(ins_impdeps "")
   foreach(arg ${ARGN})
     list(APPEND ins ${CMAKE_CURRENT_SOURCE_DIR}/${arg})
+    list(APPEND ins_impdeps CXX)
+    list(APPEND ins_impdeps ${CMAKE_CURRENT_SOURCE_DIR}/${arg})
   endforeach()
 
   # Get local include directories for atdna
@@ -50,9 +56,23 @@ macro(atdna out)
   endif()
 
   # Make target
-  add_custom_command(OUTPUT ${out} COMMAND $<TARGET_FILE:atdna> 
-                     ARGS ${extraargs} -o ${out} ${cdefcli} ${inccli} "-I${ATHENA_INCLUDE_DIR}"
-                     -isystem "@CONF_CLANG_INCLUDE_DIR@" ${ins}
-                     DEPENDS ${ins} COMMENT "Generating DNA ${out}")
+  if(${CMAKE_GENERATOR} STREQUAL "Ninja")
+    # Use Ninja's DEPFILE parser in cooperation with atdna
+    add_custom_command(OUTPUT ${out} COMMAND $<TARGET_FILE:atdna>
+                       ARGS ${extraargs} -o ${out_rel} -MD -MT ${out_rel} -MF ${out_rel}.d ${cdefcli} ${inccli}
+                       "-I${ATHENA_INCLUDE_DIR}" -isystem "${CLANG_INCLUDE_DIR}" ${ins}
+                       DEPENDS atdna ${ins} IMPLICIT_DEPENDS ${ins_impdeps}
+                       DEPFILE "${CMAKE_CURRENT_BINARY_DIR}/${out}.d"
+                       WORKING_DIRECTORY ${CMAKE_BINARY_DIR}
+                       COMMENT "Generating DNA ${out_rel}")
+  else()
+    # Use CMake's built-in dependency scanner for makefile targets
+    add_custom_command(OUTPUT ${out} COMMAND $<TARGET_FILE:atdna>
+                       ARGS ${extraargs} -o ${out_rel} ${cdefcli} ${inccli}
+                       "-I${ATHENA_INCLUDE_DIR}" -isystem "${CLANG_INCLUDE_DIR}" ${ins}
+                       DEPENDS atdna ${ins} IMPLICIT_DEPENDS ${ins_impdeps}
+                       WORKING_DIRECTORY ${CMAKE_BINARY_DIR}
+                       COMMENT "Generating DNA ${out_rel}")
+  endif()
 endmacro()
 
diff --git a/atdna/main.cpp b/atdna/main.cpp
index 820bf6b..41b66e9 100644
--- a/atdna/main.cpp
+++ b/atdna/main.cpp
@@ -4,6 +4,7 @@
 #include "clang/AST/RecursiveASTVisitor.h"
 #include "clang/Frontend/CompilerInstance.h"
 #include "clang/Frontend/FrontendAction.h"
+#include "clang/Frontend/Utils.h"
 #include "clang/Tooling/Tooling.h"
 #include "clang/Lex/Preprocessor.h"
 #include "clang/Sema/Sema.h"
@@ -61,6 +62,14 @@ static llvm::cl::list<std::string> SystemIncludeSearchPaths("isystem",
 static llvm::cl::opt<std::string> StandardCXXLib("stdlib",
                                                  llvm::cl::desc("Standard C++ library"));
 
+static llvm::cl::opt<bool> DepFile("MD", llvm::cl::desc("Make Dependency file"));
+
+static llvm::cl::opt<std::string> DepFileOut("MF",
+                                             llvm::cl::desc("Dependency file out path"));
+
+static llvm::cl::list<std::string> DepFileTargets("MT",
+                                                  llvm::cl::desc("Dependency file targets"));
+
 static llvm::cl::list<std::string> SystemIncRoot("isysroot",
                                                  llvm::cl::desc("System include root"));
 
@@ -2372,11 +2381,20 @@ class ATDNAAction : public clang::ASTFrontendAction
         return {};
     }
 
+    std::unique_ptr<clang::DependencyFileGenerator> TheDependencyFileGenerator;
+
 public:
-    explicit ATDNAAction() {}
+    explicit ATDNAAction() = default;
     std::unique_ptr<clang::ASTConsumer> CreateASTConsumer(clang::CompilerInstance& compiler,
                                                           llvm::StringRef /*filename*/)
     {
+        clang::DependencyOutputOptions DepOpts;
+        DepOpts.OutputFile = DepFileOut;
+        DepOpts.Targets = DepFileTargets;
+        if (!DepOpts.OutputFile.empty())
+            TheDependencyFileGenerator.reset(
+                clang::DependencyFileGenerator::CreateAndAttachToPreprocessor(compiler.getPreprocessor(), DepOpts));
+
         std::unique_ptr<StreamOut> fileout;
         StreamOut* fileoutOld;
         if (OutputFilename.size())
@@ -2406,7 +2424,8 @@ int main(int argc, const char** argv)
         args.push_back(argv[a]);
 
     llvm::IntrusiveRefCntPtr<clang::FileManager> fman(new clang::FileManager(clang::FileSystemOptions()));
-    clang::tooling::ToolInvocation TI(args, new ATDNAAction, fman.get());
+    ATDNAAction* action = new ATDNAAction();
+    clang::tooling::ToolInvocation TI(args, action, fman.get());
     if (!TI.run())
         return 1;