Background: Post-operative nausea and vomiting (PONV) are a common problem associated with general anesthesia. The incidence in high-risk patients can be about 80%. Objective: The objective was to compare aprepitant versus ondansetron and aprepitant combination antiemetic therapy as regards the efficacy and duration of the combination of dexamethasone-ondansetron as a gold stander and dexamethasone-aprepitant versus dexamethasone-ondansetron-aprepitant in patients undergoing laparoscopic bariatric surgery. Patients and Methods: A prospective, double-blinded, randomized control clinical trial, for evaluation of 150 laparoscopic bariatric surgery patients receiving a standardized general anesthetic; patients in the dexamethasone- ondansetron Group A (Group DO, n=50) received oral placebo identical to aprepitant 2 hours before the induction of anesthesia then ondansetron 4 mg IV within the last 30 minutes of operation. In the dexamethasone-aprepitant Group B (Group DA, n=50) the patients received 80 mg orally aprepitant 2 hours before the induction of anesthesia and 2 ml saline intravenously (IV) within the last 30 minutes of surgery. Patients in the dexamethasone-ondansetron- aprepitant Group C (Group DOA, n=50) received oral aprepitant 2 hours before the induction of anesthesia and then 4 mg ondansetron IV within the last 30 minutes of operation. We were given 8 mg dexamethasone IV after the induction of anesthesia to all patients. The primary outcome measured the severity of nausea with complete response (no PONV and no rescue antiemetics) up to 48 h postoperatively. The secondary outcome measure was the amount of rescue postoperative antiemetics given during the first 48 h postoperatively. Result: Nausea severity was higher in Group A (the Group DO) more than Group B (Group DA) more than Group C (Group DOA). The mean of nausea verbal rating score in the Group B was lower than Groups A, but no statistically significant but, in the Group C was more lower and statistical significance in compared with Group A and B at 4 h, 8 h, 12 h, 16 h, 20 h, 24 h and 48 h (p