Total intravenous anaesthesia (TIVA) can reduce the risk of postoperative nausea and vomiting (PONV) almost as much as a single antiemetic. This study compared TIVA (using propofol and remifentanil) with prophylactic palonosetron (a 5-hydroxytryptamine type 3 receptor antagonist) combined with inhalation anaesthesia using sevoflurane in 50% nitrous oxide, for the prevention of PONV. Patients were randomly assigned to one of two prophylactic interventions: (i) palonosetron 0.075 mg, intravenously before induction of inhalation anaesthesia (palonosetron group); and (ii) TIVA (propofol target blood concentration 2.5-6.0 μg/ml; remifentanil target blood concentration 2.5-6.0 ng/ml; TIVA group). Nausea/vomiting occurrence and severity were monitored immediately after the end of surgery for 24 h. The incidence of PONV was around 50% in both groups and the severity of nausea was similar in both groups. Prophylactic palonosetron with inhalational anaesthesia using sevoflurane in 50% nitrous oxide reduced the incidence of PONV after gynaecological laparoscopic surgery almost as much as TIVA using propofol and remifentanil.