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Background and Objective: Nausea and vomiting are common complications after surgery which creates spasm, hypoxia and pulmonary aspiration. This study was done to determine the effect of ondansetrone, metoclopramide associated with dexamethasone on postoperative nausea and vomiting in cholecystectomy surgery using Laparoscopic method. Methods: In this double blind clinical trial study, 100 patients with ASA class I and II undergoing laparoscopic cholecystectomy divided randomly into two groups. The patients in the first group were received metoclopramide (10mg/kg/bw) with dexamethasone (8mg/kg/bw) and the second group were received ondansetron (4mg/kg/bw) with dexamethasone (8mg/kg/bw) intravenously 5 min before the final stage of surgery. Premedication and induction of anesthesia in patients were equal 5 minutes to 4 hours after surgery, postoperative nausea and vomiting were recorded for each patient. Results: The rate of nausea in the first and the second groups were recorded 38% and 28%, respectively. The rate of vomiting in the first and the second groups were recorded 30% and 16%, respectively. These values were not significant. Conclusion: Ondansetron with dexamethasone non significantly reduced postoperative nausea and vomiting after laparoscopic cholecystectomy in comparison with metoclopramide with dexamethasone.