In this prospective, randomized, double-blinded study, we compared the prophylactic efficacy of nalbuphine and ondansetron for the prevention of intrathecal morphine-induced pruritus after cesarean delivery. Two-hundred-forty parturients were randomly allocated into four groups. The N-4 group, O-4 group, O-8 group, and placebo group received IV 4 mg of nalbuphine, 4 mg of ondansetron, 8 mg of ondansetron, and 4 mL of normal saline, respectively, immediately after the baby was delivered. In the postanesthesia care unit, we found that the severity of pruritus score in the four groups was significantly different (P < 0.001). The prophylactic success rate for pruritus of the N-4, O-4, O-8, and placebo groups was 20%, 13%, 12%, and 6%, respectively (P < 0.001). The pruritus score between N-4 and placebo and O-4 and placebo was significantly different (P < 0.001 and P = 0.006, respectively). Treatment for pruritus was requested by patients in 25%, 47%, 51%, and 72% of patients in the N-4, O-4, O-8, and placebo groups, respectively (P < 0.001). There were no differences among groups in nausea/vomiting score, pain score, sedation score, or shivering score at 4, 8, and 24 h after surgery. Nalbuphine and ondansetron are more effective than placebo for the prevention of intrathecal morphine-induced pruritus after cesarean delivery.IMPLICATIONSNalbuphine and ondansetron are more effective than placebo for the prevention of intrathecal morphine-induced pruritus after cesarean delivery.