Background and objective: Ondansetron is widely used for the prophylaxis of postoperative nausea and vomiting, while haloperidol is an antiemetic that lacks recent data on efficacy and adverse effects. Methods: In this prospective, randomized, double-blinded study involving 93 females undergoing gynaecological procedures under general anaesthesia, we compared the efficacy and adverse effects of prophylactic haloperidol 1 mg intravenous and ondansetron 4 mg intravenous vs. placebo. Results: During the overall observation period (0–24 h), in the haloperidol, ondansetron and placebo groups respectively, the incidence of nausea and/or vomiting was 40.7% (11/27), 48.2% (13/27) and 55.5% (15/27), and the need of rescue antiemetics was 22.2% (6/27), 44.4% (12/27) and 40.7% (11/27), with P values >0.05 among the three groups. During the early observation period (0–2 h), in the haloperidol, ondansetron and placebo groups respectively, the incidence of nausea and/or vomiting was 13.7% (4/29), 26.6% (8/30) and 43% (13/30), and the need for rescue antiemetics was 6.8% (2/29), 26.6% (8/30) and 36.6% (11/30). Between haloperidol and placebo groups, the P value was 0.04 for nausea and/or vomiting, and was 0.01 for rescue antiemetics, in addition to lower nausea scores (P = 0.03). During the late observation period (2–24 h), no significant difference was shown among the three groups. Conclusion: The prophylactic administration of 1 mg intravenous haloperidol or 4 mg ondansetron, in female patients undergoing gynaecological surgery, did not improve the overall incidence of nausea and/or vomiting vs. placebo. However, haloperidol 1 mg proved to be an effective antiemetic in the early observation period without significant adverse effects.