If you are talking about using an external hard drive to run the Sims then that can cause a few problems. This is because each USB port is assigned a drive letter, however they are not static, therefore if you run a SD card from a camera it could cause the drive letters to jumble up and to run programs on a computer you really need a static drive letter to be consistent. The other problem is the external drive will cause the game to run slower than usual, how much slower is totally dependant on the drive type.
I would suggest that you uninstall the game, run basic clean up and maintenance, disk clean up and a defrag, then reinstall. If problem persist then come back here, there is more that enough information to go around