I am a natural lefty who was forced to eat and write right-handed. I still do a lot left-handed. That said, I think it is just awkward to use the cutters at first regardless of which hand you use. I was showing someone the other day, asked which hand she used and set it up backwards anyway. We just turned the cutting mat around and it was set up for her. I do use the olfa cutter which is straight and works well in either hand. Obviously, the ergonomic handled ones are specific to which hand you use. I have right-handed scissors because the left is awkward for me but I naturally grab the rotary cutter with the left. Go figure.