Not all external drives are created equally - nor the interface. I have a Core2 quad downstairs with Windows 7 and an older USB WD 500Gig "My Book" drive. I cannot run SH4 from that. It is too slow. Same machine booted into Windows 10, and using a USB2 HD caddy with an older 500gig, 5400rpm laptop drive, and it does fine. It still doesn't run as well as the internal 720rpm drives, of course.
You did not mention your source of the game, the path to your game's install, or your version of Windows. You do have to experiment with those Properties settings though. If Vista compatibility does not work, then try Windows XP SP2. You might also have to use the "Run as an administrator" option.
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