Purpose: Post-operative nausea and vomiting (PONV) remains the most frequently reported patient complaint after anesthesia. Aprepitant is the first neurokinin-1(NK1) receptor antagonism available for use as an antiemetic. We investigated whether aprepitant can effectively decrease PONV in patients undergoing laparoscopic gynecological surgery. Methods: Sixty four patients receiving general anesthesia for laparoscopic gynecological surgery were randomly assigned to either receive a preoperative dose of 80 mg aprepitant or no drug. Efficacy was assessed in 2 and 24 hours after surgery. Primary and secondary endpoints were analyzed for the time intervals 0-2 hours (acute phase) and 2-24 hours (delayed phase). Vomiting, nausea, use of rescue anti-emetic, and visual analog scale (VAS) were assessed. Nausea was assessed on a 4-point scale, from 0 to 3. Results: Sixty patients participated in the study. At acute phase, PONV was present in both control and NK1 group and were 63% and 43% respectively. The severity of nausea was much less in the NK1 group. PONV prevalence at delayed phase was present in control but absent in NK1 group 27% vs. 0%, respectively. The amount of pain medication used by patients in the NK1 group was significantly less for diclofenac and pentazocine suggesting increase pain tolerance. Conclusions: Neurokinin-1 receptor antagonism effectively lowered PONV increased pain tolerance, and expedited recovery in patients undergoing laparoscopic gynecological surgery. J. Med. Invest. 58: 246-251, August, 2011