Yes. There is a difference. DVI is, for the most part, a cleaner signal than VGA. Having said that, there are also other factors that will affect picture quality like the video card ( quality of the components ), LCD type, even cable type / quality. You probably won't notice much difference between the two when gaming except maybe differences in color. Generally, the newer panels do a better job with signal noise but there is still some extra noise present in VGA. You will see this right away by putting your LCD in DualView clone mode and running a pattern generator ( Passmark's Monitor Test ) and switching between DVI and VGA. I have both a Dell 2001FP and 2405FPW and the 2405FPW and the difference is much greater on the 2001FP than the 2405FPW.