Ergotamine tartrate and methysergide are widely used headache treatments with important vasoconstrictive properties. We report a 31-year-old man with cluster headaches who developed severe, prolonged myocardial ischemia following combination therapy with ergotamine tartrate and methysergide. We reviewed the cardiovascular complications of each agent alone and in combination. Given the pharmacologic similarity of these agents, we propose that they may have additive or synergistic cardiac toxicity, at least in vulnerable individuals. We recommend caution when these agents are used together.