We have reviewed randomized controlled trials to assess the effectiveness and safety of anaesthetics which omitted nitrous oxide (N2O) to prevent postoperative nausea and vomiting (PONV). Early and late PONV (6 and 48 h after operation, respectively), and adverse effects were evaluated using the numbers-needed-to-treat (NNT) method. In 24 reports with information on 2478 patients, the mean incidence of early and late vomiting with N2O (control) was 17% and 30%, respectively. Omitting N2O significantly reduced vomiting compared with a N2O regimen; the combined NNT to prevent both early and late vomiting with a N2O-free regimen was about 13 (95% confidence intervals (CI) 9, 30). The magnitude of the effect depended on the incidence of vomiting in controls. In studies with a baseline risk higher than the mean of all reports, the NNT to prevent both early and late vomiting with a N2O-free anaesthetic was 5 (95% CI 4, 10). When the baseline risk was lower than the mean, omitting N2O did not improve outcome. Omitting N2O had no effect on complete control of emesis or nausea. The NNT for intraoperative awareness with a N2O-free anaesthetic was 46 compared with anaesthetics where N2O was used. This clinically important risk of major harm reduces the usefulness of omitting N2O to prevent postoperative emesis.