OBJECTIVES: To investigate whether the 5-HT3 receptor antagonists—ondansetron, granisetron, tropisetron, and dolasetron—used for the prevention of post-operative nausea and vomiting (PONV) differ in efficacy. METHODS: A meta-analysis was conducted using published studies. A systematic literature search within Pubmed and the Cochrane Library for randomized, controlled, double-blinded studies measuring efficacy in terms of PONV prophylaxis was conducted. The odds of patients exempted from PONV and post-operative vomiting (POV) within each study arm 24 hours after surgery were the primary indices of drug efficacy. Indirect comparisons using random effect models were conducted. Subgroup analyses excluding controversial studies and controlling amount of dose and administration route were also conducted. RESULTS: A total of 82 studies were identified, representing 15,709 patients. In terms of preventing PONV, the analysis indicated that granisetron was statistically significantly better than ondansetron (odds ratio(OR)=1.46, 95% confidence interval(CI):1.08-2.00) and dolasetron(OR=1.56, 95%CI: 1.03-2.34); no other statistically significant relationships comparing either two of the four drugs were found. In terms of preventing POV, the four antiemetic drugs had comparable efficacy: granisetron showed similar efficacy as compared to ondansetron(OR=1.61, 95%CI: 0.99-2.63), tropisetron(OR=1.70, 95%CI: 0.95-3.05) and dolasetron(OR=1.35, 95%CI: 0.78-2.27); ondansetron exhibited comparable efficacy as compared to tropisetron(OR=1.06, 95%CI: 0.63-1.79) and dolasetron(OR=0.84, 95%CI=0.52-1.31); tropisetron and dolasetron were also similar in efficacy(OR=0.80, 95%CI=0.44-1.37). Subgroup analyses also found that the four drugs did not differ in efficacy. All 5-HT3 receptor antagonists were statistically significantly better than placebo. CONCLUSIONS: With respect to PONV prophylaxis, granisetron was statistically significantly better than ondansetron and dolasetron; ondansetron, tropisetron, and dolasetron exhibit similar efficacy. With respect to POV prophylaxis, ondansetron, granisetron, tropisetron, and dolasetron appeared to have comparable efficacy.