To assess the efficacy of 4 mg of intravenous ondansetron versus placebo for the prevention of postoperative nausea and vomiting (PONV) in cholecystectomy, a type of surgery that is highly emetic. A random, double blind, placebo controlled study of 40 women over 18 years of age who were scheduled for non urgent laparoscopic cholecystectomy under general anesthesia. The patients were assigned to two groups to receive ondansetron (n = 23) or placebo (n = 17). Premedication and anesthesia were similar for all. The severity of PONV in the first 24 hours after surgery was recorded. There were no significant differences between the two groups with respect to biological characteristics or other factors that might influence the presentation or severity of PONV. The percentage of PONV-free patients was significantly higher in the ondansetron group than in the control group (73.91 and 11.76%, respectively; p < 0.001). Intravenous administration of 4 mg ondansetron is significantly superior to placebo for PONV prophylaxis after laparoscopic cholecystectomy.