IIRC Windows XP 64-bit was supposed to be a pure 64-bit OS - no compatibility layer for 32-bit apps. Which is most of the reason it didn't get some great adoption.
Later versions of 64-bit Windows had that compatibility layer.
Windows XP 64 Bit Edition was 64-bit only and ran on Intel Itanium processors. Windows XP Professional 64 Bit Edition ran on AMD64 architecture and included 32-bit compatibility with x86 Windows, but not 16-bit compatibility with DOS. It provided a preview of the broken drivers that were part of the Vista rollout.
64-bit XP ran 32 bit apps just fine. A little more than a decade ago I built a machine with it, and wound up giving it to my very much non techie parents who had no issues with it.
I think the only thing I had trouble with on that machine was finding drivers for a particular printer.
Later versions of 64-bit Windows had that compatibility layer.