OBJECTIVE To compare intravenous dexamethasone and ondansetron for the prophylaxis of postoperative nausea and vomiting (PONV), a main complaint that affects almost 40%-75% of patients undergoing laparoscopic gynecologic surgery. METHODS In a prospective study, 93 women were divided into 3 groups receiving 4mg of dexamethasone, 8mg of dexamethasone, or 4mg of ondansetron. PONV score was used for assessment during the first 24hours after surgery. RESULTS The incidence of PONV during the 24-hour postoperative period was highest in the ondansetron group (61%). In the first 3hours, the incidence of PONV in the ondansetron group was also higher: 51.6% as compared with 22.6% and 36.6% in the dexamethasone 4mg and 8mg groups, respectively. The overall incidence of PONV was highest in the first 3hours as compared with later time periods, and there was a linear trend in decreasing PONV among the groups (P=0.017). In the dexamethasone 4mg group, the request for a rescue antiemetic was significantly lower: 0% as compared with 6.7% and 16.1% in the dexamethasone 8mg and ondansetron 4mg groups, respectively. CONCLUSIONS Dexamethasone was found to be an efficacious and cost-effective drug for the prophylaxis of PONV.