We conducted a prospective, randomized, double-blind clinical trial comparing droperidol 1.25 mg intravenously (i.v.) (group 1, n = 30), ondansetron 4 mg i.v. (group 2, n = 30), or both (group 3, n = 30) in the prevention of postoperative nausea and vomiting (PONV) in the first 24 h following major gynaecological procedures under combined general and epidural anaesthesia. PONV was analysed by a linear nausea/vomiting score, incidence of nausea and vomiting, and the need for antiemetic rescue. Our results showed a similar incidence of nausea and vomiting in all groups (G1 33%, G2 40%, G3 43%). However, when comparisons were made according to the time of assessment, combination therapy resulted in significantly lower PONV than droperidol in the first hour (0% vs. 13%, P < 0.05) and second hour (0% vs. 13%, P < 0.05), and than ondansetron on the first hour (0% vs. 13%, P < 0.05). A trend persisted up to the fourth hour but was not statistically significant in either group. In conclusion, droperidol and ondansetron are effective agents in the prevention of PONV, and their combination seems to provide slightly better results than either drug alone.