I use a Tube Screamer (reissue) with an American Deluxe Strat and a 1968 Les Paul Custom and a Fender 1965 black-face Super Reverb. You should be aware that the Tube Screamer responds very differently to single-coil and humbucking pickups. If I need a clear tone with some edge, I use the Strat. If I need a heavier sound with full-tilt distortion, I use the Les Paul. I have to crank the amp pretty good to get serious distortion with the Strat, and that's not always possible. I really like the Tube Screamer. You might want to try the Turbo Tube Screamer which has a low-end boost that is supposed to work well with Strats.