In a SysWOW64 installation you cannot run 16-bit applications under a 64-bit Operating System. Windows on Windows cannot run another session of Windows on Windows inside one one another. In this case, you can run anything that is a 32-bit application, but older apps will require a separate, virtualizeed space to run under. Boot up a 32-bit VM and run a 16-bit program in that. As far as compatibilities go with older apps? Windows Vista 64-bit never gave any problems, nor does Windows 7. It's the 16-bit limitation that persists in many operating systems running on x64/x86_64 platforms that is the hindrance. Unless someone finds a way to emulate the environment while running it under a mode that doesn't require a full reset of the CPU (64-bit Long mode > 16-bit is NOT Native!), you're stuck with VMs.