Objective: Patients undergoing total joint replacement procedures have a remarkably high incidence of postoperative nausea and vomiting. The purpose of this study was to evaluate the efficacy and safety of ramosetron, a serotonin 5-HT3 receptor antagonist, for the prevention of nausea and vomiting after total hip replacement. Design: Prospective, randomised, double-blind, placebo-controlled study. Setting: University-affiliated teaching hospital. Patients: Eighty patients, aged 35-77 years, 22 male and 58 female, scheduled for total hip replacement. Interventions: Patients received in a randomised, double-blind manner intravenously administered placebo or ramosetron in three different doses (0.15, 0.3 or 0.6mg) at the completion of surgery (n = 20 in each group). A standard general anaesthetic technique and postoperative analgesia were used. Main outcome measures and results: Emetic episodes were recorded and safety assessments performed over 0 to 24 hours after anaesthesia. The rate of patients experiencing emetic symptoms (nausea, retching, vomiting) over 0 to 24 hours after anaesthesia was 70% with ramosetron 0.15mg (p = 0.5), 25% with ramosetron 0.3mg (p = 0.002) and 20% with ramosetron 0.6mg (p = 0.001), compared with placebo (75%). No clinically important adverse events were observed in any of the groups. Conclusion: Prophylactic antiemetic therapy with ramosetron 0.3mg is efficacious against postoperative nausea and vomiting 0 to 24 hours after anaesthesia in patients undergoing total hip replacement. Increasing the dose to 0.6mg provided no further benefit.