BACKGROUND Pruritus is the most common side effect of epidural morphine analgesia. Diphenhydramine is a widely used agent for the treatment of urticarial pruritus. Nalbuphine is a mixed opioid agonist-antagonist and has been reported to be effective in treating opioid-induced pruritus. We compared the effectiveness of intramuscular diphenhydramine and nalbuphine for the prevention of epidural morphine-induced pruritus after cesarean section. METHODS One hundred and fifty, American Society of Anesthesiologists physical status I or II, women undergoing cesarean section with epidural anesthesia were randomly assigned to three groups. Group S, group D, and group N received intramuscular normal saline (1 ml; n = 50), diphenhydramine (30 mg/1 ml; n = 50), and nalbuphine (10 mg/1 ml; n = 50), respectively, after delivery of the baby. The occurrence and the severity of pruritus were assessed at 1, 4, 12, and 24 hours after surgery. RESULTS The overall incidence of pruritus during the 24 hr follow-up period was 72%, 68%, and 44% for group S, group D, and group N, respectively. Pruritus occurred less frequently in group N than group D (p = 0.027). At 4 and 12 hrs postoperatively, the pruritus severity was significantly different (p = 0.003 and p = 0.002) and was significantly less in group N than group D in the intergroup comparison (p = 0.013 and p = 0.012). CONCLUSIONS Nalbuphine proved better than diphenhydramine for prevention of epidural morphine-induced pruritus in patients who underwent cesarean section. Prophylactic intramuscular nalbuphine (10 mg) is effective in decreasing the incidence and severity of pruritus and does not affect analgesia.