Background: Post-operative nausea and vomiting (PONV) is a frequent complication associated with laparoscopic cholecystectomy. In this randomized double-blind placebo controlled prospective study, we compared the efficacy of intravenous metoclopramide and ondansetron for prevention of PONV following laparoscopic cholecystectomy in patients. Materials and Methods: A total of 75 patients (20–60 years of age) undergoing elective laparascopic cholecysetectomy were randomly allocated to one of the three groups of 25 patients each. Group A received metoclopramide 10 mg, Group B received ondansetron and group C received normal saline 10 ml after induction. All episodes of PONV within 24 hrs. after induction of anesthesia were recorded. Results: The overall incidence of post-operative emesis was 44% in control group, 16% in Metoclopramide group and 12% in Ondansetron group.The decrease in incidence of emesis in Metoclopramide and Ondansetron group was significant as compared to control group whereas there was no statistical difference between Metoclopramide and Ondansetron groups. Conclusion: For prevention of PONV after laparoscopic cholecystectomy, both metoclopramide and ondansetron are equally effective in comparison to placebo group.