Objective: To evaluate the effectiveness of greater occipital nerve (GON) blockade in patients with acute migraines. Methods: This study was conducted on patients with acute migraines. The patients were randomly assigned into 3 groups: the GON group (bupivacaine), the placebo group (injection of normal saline), and the intravenous (IV) treatment group (dexketoprofen and metoclopramide), 30 people per group. The pain severity was assessed at 5, 15, 30, and 45 min by pain scale score. And the adverse events were recorded. Results: There was no significant difference in pain scores between the three groups at the 0th, 5th and 15th minutes of treatment (P>0.05). At 30th or 45th min, the pain score was lowest in the GON block group, and the highest in the placebo group (all P<0.05). There was no statistically significant difference in the pain scores of 0–5, 0–15 minutes between the three groups (P>0.05). At 0–30 or 0–45 minutes, the GON block group had the largest reduction in pain scores, followed by the intravenous group, and the lowest was the placebo group (all P<0.05); there were no adverse events at the injection site in the study groups during the treatment period. Conclusion: A GON blockade was superior to IV (dexketoprofen + metoclopramide) and placebo in patients with acute migraine headaches. Despite being an invasive procedure, a GON blockade might be an effective option for acute migraine treatment due to its rapid, easy, and safe application.