INTRODUCTION: Headache is the most common neurologic symptom among referees to the emergency department (ED), while the best treatment has not yet been found. Therefore, in the present study pain relief effects of metoclopramide and acetaminophen were compared in patients suffered acute primary headache. METHODS: This study was a double-blind randomized clinical trial performed in Imam Khomeini Hospital, Urmia, Iran, through July to October 2014. All adult patients, with acute primary (migraine, tension type and cluster) headache referred to the ED were included in this study. Pain severity was measured with 10 centimeters numeric rating scales. The patients were randomized into two groups of intravenous (IV) metoclopramide (10 milligrams) and acetaminophen (1 gram). Pain score, success rate, and drug complications were compared between the 2 groups at 0, 15, 30, 60, and 120 minutes after injection. RESULTS: 100 patients were equally categorized into two groups (mean age of 32 ± 13.2 years; 51.2% male). Initial pain score in metoclopramide and acetaminophen groups were 9.1 and 9.4, respectively (p = 0.46). IV metoclopramide did not have any analgesic effect at 15 minutes, but had good effect at 30 minutes. While, the analgesic effect of acetaminophen initiated after 15 minutes. After 2 hours, both drugs had good therapeutic effect on primary headaches (p < 0.001). CONCLUSION: The present study demonstrated that efficacy of metoclopramide for pain relief in primary headaches is lower than acetaminophen. In this regard, success rate of acetaminophen was 42.0% versus 0% for metoclopramide within 15 minutes. The efficacy of acetaminophen continued until 60 minutes.