Abstract To compare the efficacy of intramuscular prochlorperazine and metoclopramide in the short-term treatment of migraine headache in the emergency department, 86 eligible adult patients with moderate to severe migraine headache were evaluated prospectively at a university-affiliated community hospital. After randomization, each subject received a 2-mL intramuscular injection of sterile saline, prochlorperazine (10 mg), or metoclopramide (10 mg). No other analgesics were administered during the 60-minute study period; patient assessment of relief was followed using visual analog scales. Reduction in median headache scores was significantly better among those treated with prochlorperazine (67%) compared to metoclopramide (34%) or placebo (16%). Similarly, symptoms of nausea and vomiting were significantly relieved in the prochlorperazine group ( χ 2 = 17.1, P < .001). However, rescue analgesic therapy was necessary in the majority of patients treated with prochlorperazine ( 16 28 ) and metoclopramide ( 23 29 ) after the 60-minute study period. Although intramuscular prochlorperazine appears to provides more effective relief than metoclopramide, these results do not recommend either drug as single-agent therapy for acute migraine headache.