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Headache is a frequent complaint among the 1.4 million patients who present to US emergency departments (ED) annually following trauma to the head. There are no evidence-based treatments of acute post-traumatic headache.This was an ED-based, prospective study of intravenous (IV) metoclopramide 20 mg + diphenhydramine 25 mg for acute post-traumatic headache. Patients who presented to our EDs with a moderate or severe headache meeting international criteria were enrolled and followed by telephone 2 and 7 days later. The primary outcome was “sustained headache relief” (headache level less than “moderate” in the ED, no additional headache medication, and no relapse to headache worse than “mild”).We also gathered data on associated symptomotology using the validated Post Concussion Symptom Scale (PCSS).21 patients were enrolled. Twelve of 20 (60%) patients with available follow-up data reported sustained headache relief. All but one of the 21 enrolled patients (95%) reported improvement of headache to no worse than mild. Seven of 19 (37%) patients with available data reported moderate or severe headache during the 48 h after ED discharge. One week later, 5/19 patients reported experiencing headaches “frequently” or “always”. The mean Post Concussion Symptom Score improved from 47.5 (SD 29.4) before treatment to 10.9 (SD 14.8) at the time of ED discharge and 11.4 (SD 21.4) at one week after treatment.IV metoclopramide 20 mg + diphenhydramine 25 mg is an effective and well-tolerated medication regimen for patients presenting to the ED with acute post-traumatic headache, though 1/3 of patients report headache relapse after ED discharge and 1/4 of patients report persistent headaches one week later.