STUDY OBJECTIVE: We compare prochlorperazine 10 mg intravenously versus metoclopramide 20 mg intravenously for the emergency department (ED) treatment of acute migraine. METHODS: This was a randomized, double-blind, clinical trial comparing 2 parenteral dopamine antagonists. Both drugs were administered during 15 minutes with 25 mg intravenous diphenhydramine. Pain scores on a numeric rating scale were assessed at baseline, every 30 minutes for 2 hours, and by telephone 24 hours after discharge. The primary endpoint was the between-group difference in change in numeric rating scale from baseline to 1 hour postbaseline. Secondary endpoints included mean differences in change in numeric rating scale at 2 and 24 hours, headache relief, adverse effects, and desire to receive the same treatment for future migraines. RESULTS: Of 152 patients screened, 97 were eligible and 77 were randomized. The mean change in numeric rating scale scores at 1 hour was 5.5 and 5.2 in subjects receiving prochlorperazine and metoclopramide, respectively (difference=0.3; 95% confidence interval [CI] -1.0 to 1.6). Findings were similar at 2 hours and 24 hours. Forty-six percent (18/39) of prochlorperazine and 32% (12/38) of metoclopramide subjects reported adverse events (difference=15%; 95% CI -6% to 36%). Seventy-seven percent (26/34) of prochlorperazine and 73% (27/37) of metoclopramide subjects wanted to receive the same medication in future ED visits (difference=4%; 95% CI -16% to 24%). CONCLUSION: Either prochlorperazine 10 mg intravenously or metoclopramide 20 mg intravenously, combined with diphenhydramine 25 mg intravenously, is an efficacious treatment for ED patients with acute migraine. Three quarters of subjects in both arms would want the same medication for their next migraine.