We have observed that patients, after retromastoid craniectomy (RMC) with microvascular decompression (MVD) of cranial nerves, frequently experienced postoperative nausea and vomiting (PONV). The authors conducted this study to track the incidence of PONV and to identify potential factors for PONV after RMC with MVD. Medical records from 185 adults, who underwent elective RMC with MVD, were identified and reviewed from January 2000 to December 2004. Extracted data included patient, anesthesia, and surgery related variables that were considered to have a possible effect on the patients experiencing PONV after RMC with MVD. Despite the use of intraoperative prophylactic ondansetron in 99% of patients, the overall incidence of PONV (nausea or emesis or both) was 60% during the first 24 hours postoperatively. It was higher for the patients after RMC with MVD of cranial nerve V [69%, 82/119, P=0.005, odds ratio (OR)=2.8]. Regression modeling demonstrated that female sex (OR=3.0, P=0.005) and use of desflurane (OR=2.8, P=0.003) were significant independent predictors of PONV. Prophylactic transdermal scopolamine patch administered preoperatively was associated with less PONV (OR=0.3, P=0.001). We concluded that PONV occurs frequently in adults recovering from RMC with MVD. The results of this study suggest that it may be necessary to administer a combination of antiemetics to decrease the incidence of PONV after RMC.