Background:Postoperative nausea and vomiting (PONV) is an undesirable complication in patients undergoing general anesthesia. Combination therapy via different mechanisms of action for antiemetic prophylaxis has been warranted for effective treatment of PONV. This study was designed to compare the prophylactic antiemetic effect between midazolam combined with palonosetron (group MP) and palonosetron alone (group P) after laparoscopic cholecystectomy surgeries.Methods:A prospective randomized controlled trial was investigated in non-smoking female. Eighty-eight patients were randomly divided into 2 groups with 44 patients each. Group MP received 0.05 mg/kg of midazolam intravenously before induction of anesthesia whereas group P received the same volume of normal saline. Immediately after anesthetic induction, 0.075 mg of palonosetron was administered to both the groups. The incidence and severity of PONV were assessed during 2 time intervals (0–2 hours, 2–24 hours), postoperatively.Results:The incidence of PONV during 24 hours after surgery was lower in group MP as compared to group P. There was also a significant difference in the use of rescue antiemetics. The severity of nausea was significantly lower in group MP as compared to group P, in the initial 2 hours after surgery. The incidence of side effects was similar between the 2 groups.Conclusion:In the prevention of PONV, midazolam combined with palonosetron, administered during induction of anesthesia was more effective as compared to palonosetron alone.