Yes, I am currently running 4 monitors with a 4870x2 and a 4870. Keep in mind though that you won't be able to use Xfire AND 4 monitors at the same time (only 2). What works for me is having one parition that I just use for games, and another that I use for everything else. I have Crossfire always enabled in the game parition, and always off for the applications parition (you could just enable, disable crossfire as needed as well)