Objectives: Pain management is an important issue in traumatic patients. The aim of this randomized clinical trial was to compare the analgesic effect of intravenous acetaminophen with intravenous morphine sulfate in patients with traumatic diaphyseal long bone fracture. Methods: This double-blind randomized clinical trial was carried out in an academic trauma center in Mashhad, Iran, from February to October 2013. After primary modalities like limb elevation, ice and limb splinting, patients were allocated to receive either acetaminophen 15 mg/kg or morphine sulfate 0.1 mg/kg randomly. The pain severity was measured using a visual analogue scale before drug administration and 5 and 30 minutes after drug administration. Then, the results were compared. Results: Of the 50 patients recruited over 9 months 26 patients received intravenous morphine sulfate and 24 patients received intravenous acetaminophen. A significant difference was observed between the two groups at 5 minutes after drug administration; the morphine sulfate group showed more reduction in pain severity after 5 minutes (P < 0.0001). However, there was no significant difference in pain severity at 30 minutes after drug administration between the two groups (P = 0.85). Conclusions: It seems that after 30 minutes, intravenous acetaminophen is as effective as intravenous morphine sulfate in pain management of isolated diaphyseal long bone fracture. However, it should be noted that the analgesic effect of acetaminophen begins with a delay. Thus, we suggest using intravenous acetaminophen when morphine administration is contraindicated.