Sumatriptan is widely prescribed for the treatment of migraine headaches. Its actions are mediated via agonist action on the vascular 5-hydroxytryptamine 1 receptor which results in vasoconstriction. We report a case of a 46-year-old woman who developed ischemic colitis while taking increasing doses of sumatriptan for a migraine headache. Her only other medication was oral contraceptives. Interestingly, a potential synergistic action between the two medications may exist since estrogen reduces triptan clearance through its action on monamine oxide, an enzyme that metabolizes serotonin. Sumatriptan should be recognized as an important cause of drug-induced colonic ischemia, especially in patients taking estrogen.