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Background: Greater occipital nerve block (GONB) is thought to be an effective treatment for acute migraine, though no randomized efficacy data have been published for this indication. We hypothesized that bilateral GONB with bupivacaine would provide greater rates of headache freedom than a sham injection among a population of emergency department (ED) patients who reported persistence of moderate or severe headache despite standard treatment with intravenous metoclopramide., Methods: This was a randomized clinical trial conducted in 2 urban EDs. Patients with acute migraine who reported persistence of a moderate or severe headache for at least 1 hour or longer after treatment with 10 mg of intravenous metoclopramide were randomized to bilateral GONB with a total of 6 mL of 0.5% bupivacaine or bilateral intradermal scalp injection with a total of 1 mL of 0.5% bupivacaine. The primary outcome was complete headache freedom 30 minutes after the injection. An important secondary outcome was sustained headache relief, defined as achieving a headache level of mild or none in the ED and maintaining a level of mild or none without the use of any additional headache medication for 48 hours., Results: Over a 31 month period, 76 patients were screened for participation and 28 were enrolled, of whom 15 received sham injection and 13 received GONB. This study was stopped before achieving the a priori sample size due to slow enrollment. The primary outcome - headache freedom at 30 minutes - was achieved by 0/15 (0%) of patients in the sham arm and 4/13 (31%) of patients in the GONB arm (95%CI for difference of 31%: 6, 56%, P = .035). The secondary outcome, sustained headache relief for 48 hours, was reported by 0/15 sham patients (0%) and 3/13 (23%) GONB patients (95% CI for difference of 23%: 0, 46%, P = .087). Reported side effects did not differ substantially between the groups., Conclusion: GONB may be an effective treatment for ED patients with acute migraine who continue to suffer from moderate or severe headache after administration of intravenous metoclopramide; however, this study was stopped prior to achieving the a priori sample size., (© 2018 American Headache Society.)