I'm not sure about different size monitors. I know you have to set each monitor to the same resolution. I made sure to get 3 identical monitors to minimize any issues. You should have the Catalyst software for your video card. It helps you set up the 3 monitors. You also have get a special adapter for your 3rd monitor. I'm at work now so I don't know exactly what it is called from memory. I also went to ATI website and downloaded instructions for helping in setting them up.