In a prospective, randomized, double-blind clinical trial, intravenous prochlorperazine edisylate (Compazine Edisylate) was compared with a placebo in the treatment of severe headaches. Eighty-two adult patients with vascular or tension-type headaches were identified at the time of presentation to one of three participating emergency departments. After the patient gave informed consent, a 2-mL intravenous injection of sterile saline solution or prochlorperazine edisylate (10 mg) was given to each patient at the time of randomization. The treatment groups were similar with regard to age, sex, and type and duration of headache. Within 60 minutes after injection, 74% (31/42) of those who received prochlorperazine had complete relief; 14% (6/42) of the patients had partial relief. Overall, there was complete or partial relief of pain in 88% (37/42) of the drug group and in 45% (18/40) of the placebo group. This difference was statistically significant using χ2 analysis. Adverse effects were minimal; one patient experienced asymptomatic orthostatic hypotension. These results suggest that intravenous prochlorperazine is an effective treatment for patients with severe vascular or tension headaches who present to the emergency department.