We compared the antiemetic efficacy of aprepitant plus palonosetron versus aprepitant plus ramosetron in patients after laparoscopic cholecystectomy. A total of 88, nonsmoking, female patients undergoing laparoscopic cholecystectomy were randomly allocated to 2 groups of 44 each who received palonosetron 0.075 mg (aprepitant plus palonosetron group) and ramosetron 0.3 mg (aprepitant plus ramosetron group) after induction of anesthesia. All patients received aprepitant 80 mg 2 hours before surgery. The incidence of postoperative nausea and vomiting (PONV), use of rescue antiemetic, pain severity, and any side effects were assessed for 24 hours after surgery. The incidence of PONV and use of rescue antiemetic were less in aprepitant plus palonosetron group than in aprepitant plus ramosetron group for 24 hours after surgery (P<0.05, respectively). There was no difference in pain severity and side effects including headache and drowsiness. Aprepitant plus palonosetron significantly prevents PONV, compared with aprepitant plus ramosetron in patients at high risk for PONV after laparoscopic cholecystectomy.