The anti-emetic efficacy of prophylactic ondansetron and tropisetron in combination with a low dose of droperidol in patients with high probability for post-operative nausea and vomiting undergoing gynaecological laparoscopy was compared. Patients were randomly allocated in a double-blind manner to receive either ondansetron 8 mg (n = 45) or tropisetron 5 mg (n = 43) at the end of surgery. A standardized general anaesthetic technique was used, including droperidol 0.75 mg. The incidence of nausea was 36% and 49% (P = 0.28), and vomiting occurred in 13% and 14% of the patients in the ondansetron and tropisetron groups, respectively. The onset time for rescue medication was significantly sooner after tropisetron than ondansetron (3 h 18 min vs. 6 h 25 min; P = 0.007). There were no statistically significant differences in efficacy between prophylactic ondansetron and tropisetron combined with droperidol in a high-risk population. However, ondansetron appeared to be more effective in preventing post-operative nausea and vomiting in the early hours after surgery compared with tropisetron.