Purpose:Patients undergoing middle ear surgery experience variable degrees of postoperative nausea and vomiting (PONV) despite prophylaxis and treatment with ondansetron or other 5HT3 receptor antagonists. Furthermore vertigo or dizziness are not well controlled perioperatively. Role of betahistine was tested as an add-on to ondansetron in control of PONV and vertigo in middle ear surgery cases.Materials and Methods:We conducted a prospective, randomized, double-blind, placebo controlled study, enrolling one hundred patients undergoing middle ear surgery under local anesthesia into two groups consisting of fifty (n = 50) patients each. Group A patients were given betahistine 16 mg plus ondansetron 8 mg and placebo plus ondansetron 8 mg were given to group B or placebo group, orally 3 hours before starting operation. The incidence of nausea, vomiting, and dizziness was noted during the intraoperative and postoperative 24 hours period. Chi-square test, unpaired ‘t’ test, and Fisher’s exact tests were performed for statistical analysis using SPSS version 16 and Open Epi version 2.3.1 softwares.Results:Complete response was obtained in 90% patients in the betahistine group as compared to 66% in the placebo group. Vomiting in the intraoperative and postoperative period was noted in 4% and 8% cases, respectively, in the betahistine group as compared to 18% and 26%, respectively, in the placebo group. Overall, vertigo was 10% versus 32% in betahistine group and placebo group, respectively.Conclusion:Betahistine as an add-on to ondansetron can significantly attenuate PONV and perioperative vertigo, following middle ear surgeries.