BACKGROUND: The purpose of this study was to compare the effects of ondansetron and granisetron on the prevention of postoperative nausea and vomiting (PONV) in gynecologic patients. METHODS: In a randomized placebo-controlled study, 200 gynecologic patients were divided into 5 groups. Each patient received one of 5 medications: placebo (saline 3 ml), ondansetron 4 mg (O4), ondansetron 8 mg (O8), granisetron 1.5 mg (G1.5) and granisetron 3 mg (G3). They were administered intravenously immediately before the induction of anesthesia. A standardized inhalation anesthesia and a postoperative intravenous patient-controlled analgesia were applied. Twenty four hours after anesthesia, the incidence and severity of PONV and other adverse effects were assessed. RESULTS: The incidence of PONV was 88%, 83%, 75%, 70% and 60% in the placebo, O4, O8, G1.5 and G3 groups, respectively, which showed significantly lower value in the G3 group than in the placebo and O4 groups (P< 0.05). The severity of PONV was also significantly lower in the G3 group than in the placebo group (P < 0.05). CONCLUSIONS: In this study, granisetron 3 mg showed a better prophylactic effect in the mitigation of PONV in gynecologic patients then a placebo or ondansetron 4 mg.