Should I define both _WIN32 and _WIN64 in 64bit build?

You should never define either of them.

The toolchain (compiler + system headers) will define them as appropriate.

The documentation for the predefined macros says:

_WIN32: Defined for applications for Win32 and Win64. Always defined.

_WIN64: Defined for applications for Win64.

So not only should _WIN32 always be defined, it does not cause any problem in 64-bit applications. Therefore, I'd suggest you don't remove it.

_WIN32：Defined for applications for Win32 and Win64. Always defined.

_WIN64：Defined for applications for Win64.

More detail: Predefined Macros .

To put it simply, WIN32/_WIN32 is used to tell whether you are using Windows(For crossing system application), while _WIN64 is used to tell the compiling environment is x86 or x64.

If you want to know whether your application is running under Windows x64, you should use Windows API IsWow64Process .

_WIN32 doesn't mean what you think it does. It means "I am using the Windows API". The 32 postfix was added back in the days of Windows NT 3.1 to make it distinct from the 16-bit API that was used in Windows version 3. This term has fallen out of favor because of the bitness problem. You can see this at stackoverflow.com, the [win32] tag takes you to [winapi].

Don't remove it, you are using the Windows API.