Background: A combination of antiemetic drugs could be an effective method to prevent severe postoperative nausea and vomiting (PONV). Therefore, we examined the prophylactic effect of haloperidol plus ondansetron on PONV. Methods: We enrolled 210 patients (n=70 in each of 3 groups) undergoing elective laparoscopic cholecystectomy for this randomized double-blind study. Patients were randomized to intravenous saline 2mL and intramuscular haloperidol 2 mg (Group H), intravenous ondansetron 4mg and intramuscular saline 2mL (Group O), or intravenous ondansetron 4mg and intramuscular haloperidol 2mg (Group H+O), administered after induction of general anesthesia and 30 minutes before the conclusion of surgery. We compared the complete response rates, incidence of PONV, nausea scores, the need for rescue medication, patient satisfaction scores, and adverse events during the 24-hour study. Results: The H+O group had the highest complete response rate to treatment (79%) compared with group H (61%) and group O (62%) (P<0.05 for both). Patient satisfaction scores were significantly higher in the H+O group (8.3�1.8) than in the H (7.0�2.4) and O (7.2�2.5) groups (P<0.05 for both). In addition, nausea scores were significantly lower in the H+O group (1.2�2.6) than in the H (2.5�3.3) and O (2.2�3.1) groups (P<0.05 for both). Conclusion: We conclude that the combination of prophylactic haloperidol (2mg) plus ondansetron (4mg) provides a higher complete response rate and greater patient satisfaction after laparoscopic cholecystectomy than either drug used alone.