Firstly, I'm not even sure if this is in the right section. You don't give any information whatsoever about why it doesn't work. Does it crash? Is there an error? Does it just not open? Does it open then close quickly? I use Vista 32 and it works fine for me. I've had it running fine on Vista 64 too. As far as I know it also works in Windows 7 without any issues. Have you enabled (Or is it enabled by default into vista 64) DEP for all processes? Add Diablo II (Diablo II.exe and game.exe) to the exceptions for DEP, reboot and try it again. If it doesn't work try patching to the latest patch (Blizzard have removed the copy protection from the latests patches which could stop it from working with your configuration).