BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication after anesthesia and surgery; 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists have been considered as a first-line therapy. Ramosetron and palonosetron are more recently developed drugs and have greater receptor affinity and a longer elimination half-life compared with older 5-HT3 receptor antagonists. The purpose of this study was to determine which drug is more effective for preventing PONV between ramosetron and palonosetron. METHODS: We enrolled 100 patients undergoing gynecological laparoscopic surgery into this study. The subjects were divided into ramosetron group and palonosetron group. The medications were provided immediately before the induction of anesthesia. The occurrence of nausea and vomiting, severity of nausea according to a visual analogue scale, and rescue anti-emetic drug use were monitored immediately after the end of surgery and at 0-6 h, 6-24 h, and 24-48 h post-surgery. RESULTS: The incidence of vomiting was significantly lower in the palonosetron group than in the ramosetron group during 0-6 h (6% vs 26%, P = 0.012) and 0-48 h (14% vs 34%, P = 0.034). The incidence of nausea and overall PONV, and the use of rescue antiemetic were not significantly different during all time intervals. The severity of nausea was not different between the two groups. CONCLUSIONS: In conclusion, the incidence of PONV between the ramosetron and the palonosetron group have not shown the difference during 0-48 h, although palonosetron results in a lower incidence of vomiting during 0-6 h post-surgery.