There should be no reason why you want to access your computer through safe mode JUST to play a game. If your computer is unstable, then fix it. That's what safe mode is for. Instead of trying to play a game through safe mode because you're afraid of instability, you should USE safemode to make your computer more stable, THEN play the game normally. Makes sense eh? But of course, to answer your question, yes, you can do anything you want in safe mode. It's just bypasses your startup programs and keeps windows default settings. However, how are you planning to play the game without your graphics card driver up? Now that's a question for you to answer =P
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