I agree it is better to save the ondansetron for occasional or unusual nausea, and I didn't know it could cause headaches. Like most such meds, overusing them or relying on them too much is often not a good thing in the long run. I wonder if it would help with MTX nausea, but would not want to use it on a continual basis, either. I am not about to try it as my MTX nausea isn't that bad and I don't want to use up the anti-nausea pills that I have.