BACKGROUND Microvascular decompression with retromastoid craniotomy carries an especially high risk of postoperative nausea and vomiting. In this study, we compare the antiemetic efficacy of ramosetron and ondansetron in patients undergoing microvascular decompression with retromastoid craniotomy. METHODS Using balanced anesthesia with sevoflurane and remifentanil infusion, ondansetron 8 mg (group O, n = 31) or ramosetron 0.3 mg (group R, n = 31) was administered at the dural closure. The incidence and severity of postoperative nausea and vomiting, required rescue medications and the incidence of side effects were measured at post-anesthetic care unit, 6, 24 and 48 hours postoperatively. Independent t-tests and the chi-square test or Fisher's exact test were used for statistical analyses. RESULTS There were no differences in the demographic data between groups, except for a slightly longer anesthetic duration of group R (P = 0.01). The overall postoperative 48 hour incidences of nausea and vomiting were 93.6 and 61.3% (group O), and 87.1 and 51.6% (group R), respectively. Patients in group R showed a less severe degree of nausea (P = 0.02) and a lower incidence of dizziness (P = 0.04) between 6 and 24 hours. CONCLUSIONS The preventive efficacy of ramosetron when used for postoperative nausea and vomiting was similar to that of ondansetron up to 48 hours after surgery in patients undergoing microvascular decompression with retromastoid craniotomy. A larger randomized controlled trial is needed to confirm our findings.