One of the primary reasons not to use your computer whilst defragging is the problem incurred by creating non-movable files. Any file that is in use by software running on your computer can not be moved around the hard drive. So if you are running a game, many of the files that it uses will not be defragged. Because of this, the hard drive will order other files around these unmovable files, and in effect can increase fragmentation. It is for this reason that you get better defrag results (within Windows) when running in safe mode). The system will defrag the hard drive, but to be honest, if you are running games you would be better off simply not running the defrag software.