The efficacy and safety of ondansetron in preventing postoperative nausea and vomiting following major gynaecological surgery was evaluated in this multicentre, double-blind study. A total of 243 patients were randomised to receive three doses of oral ondansetron 8 mg or matching placebo at 8-hourly intervals, with the first dose being given an hour before surgery. A standard general anaesthetic technique was employed throughout. Nausea, vomiting and safety assessments were performed continuously during the 24 h postrecovery period. Of the 237 patients evaluated for efficacy, significantly fewer ondansetron 8 mg treated patients (65/117; 56%) experienced postoperative nausea and/or vomiting compared with placebo-treated patients (94/120; 78%) during the study period (p < 0.001). In addition, ondansetron 8 mg reduced the severity of nausea (p < 0.001) and the total number of vomiting episodes experienced (p < 0.001). Overall, ondansetron 8 mg was well tolerated and effective in preventing postoperative nausea and vomiting in this surgical setting.