Background. Postoperative nausea and vomiting (PONV) is a significant cause of morbidity among patients undergoing general anaesthesia. The optimal strategy for prevention of PONV, however, remains unclear. This study compared two commonly used prophylactic strategies in high-risk, day-case, gynaecological surgery patients. Methods. We conducted a randomized trial comparing sevoflurane combined with dolasetron (SD), with propofol-based total intravenous anaesthesia (TIVA) in 126 high-risk patients undergoing day-case gynaecological surgery. The primary endpoints included the incidence and severity of nausea or vomiting before discharge and the incidence of nausea or vomiting between discharge and 24 h. To identify the factors most predictive of a complete response (no PONV at any time within the 24 h period), multiple logistic regression models were fitted. Results. Before discharge, there was no significant difference between the two treatment groups with respect to nausea and vomiting outcomes (P = 0.3). Post-discharge nausea and vomiting (PDNV), however, were significantly more common for patients in the TIVA group (nausea, P = 0.004 and vomiting, P = 0.03). Type of anaesthetic, adjusted for weight and anaesthesia duration was significantly associated with complete response (odds ratio = 2.7, 95% confidence interval = 1.15 to 6.4). Conclusions. Although both TIVA and dolasetron prophylaxis reduce the predicted rate of PONV in the early postoperative period, the anti-emetic effects of propofol are short-lived. A longer-acting drug such as dolasetron may therefore be necessary to prevent PDNV.