UNLABELLED This investigation was conducted as a national multicenter study to evaluate effectiveness and safety of prophylactic and therapeutic ondansetron for postoperative nausea and vomiting (PONV) in major gynaecological surgery. METHODS 387 patients were randomised to receive either ondansetron 8 mg or placebo i.v. prior to anaesthesia induction. Anaesthesia was performed with a volatile anaesthetic, nitrous oxide and opioids. Established PONV was treated with ondansetron 4 mg i.v. Postoperative evaluation included time, duration and severeness of nausea and vomiting in the first 24 h after the operation. RESULTS In the study period the incidence of emesis was 35% after prophylactic ondansetron and 58% after placebo (p < 0.01). Nausea occurred in 49% and 64% respectively (p < 0.01). 28% after prophylactic ondansetron and 48% after placebo required ondansetron therapy (p < 0.01). The number of adverse events was small in total and comparable for both groups. CONCLUSION Our investigation proves the efficiency of ondansetron 8 mg prior to induction of anaesthesia in preventing PONV. Furthermore, our results demonstrate the safety of the drug for prophylaxis and therapy.