In theory, your drawing tablet should work just fine with any program, since it should work just like a regular mouse (but with a pen instead of a trackball/laser). You should be able to draw lines with no problem. However, in Paint.NET, you will not get the same pressure sensitivity function as you do in some other programs such as Photoshop. As of Paint.NET version 3.5, pressure sensitivity has been removed from the program (if I recall, it was due to the fact that it was very haphazardly implemented before and is going to be released again sometime in the future). All your lines will be the same thickness and opacity if you choose to use Paint.NET to draw. If you need an image-editing program that has pressure sensitivity, I point you in the direction of The GIMP, a free program which is somewhat confusingly laid out, but has a more extensive set of features.