Laparoscopic surgery provides tremendous benefits to patients, including faster recovery, shorter hospital stay and prompt return to normal activities. Despite the minimally invasive nature of laparoscopy, high incidence of postoperative nausea and vomiting remains a major challenge for anaesthetist. Postoperative nausea and vomiting (PONV) are common complications after anesthesia and surgery. Postoperative nausea and vomiting are observed in increased frequency after laparoscopic surgery. Aim: the aim of this study was to compare the efficacy of intravenous dexamethasone and intravenous ondansetron in preventing postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy. Methods: The study was designed as a hospital-based Prospective observational study 100 patients of ASA physical status I and II of either sex scheduled to elective laparoscopic cholecystectomy under general anaesthesia. The patients were randomly allocated to two equal groups of 50 each. Group A consisted of patients receiving inj. Dexamethasone 4 mg and in group B patients received inj. Ondansetron 4 mg. Hemodynamic variables were continuously monitored till the end of surgery. Post-operative nausea and vomiting were recorded at 0, 1, 6, 12, 24 hrs after the surgery. Results: The frequency of nausea was not statically significantly among the two study groups at different time intervals postoperatively. In group A, 21% of patients had nausea, as compared to 28% in group B (p >0.01). Postoperative vomiting occurred in 12.9% of patients in group A and 10.6% of patients in group B throughout the whole study period (p>0.01). There was no significant difference in the effect by dexamethasone versus ondansetron and both were equally effective against PONV and without any side effects. Conclusion: Preoperative intravenous low dose of Dexamethasone reduces the incidence of postoperative nausea and vomiting and is comparable to intravenous Ondansetron. The effects of dexamethasone and ondansetron in preventing PONV were similar after laparoscopic cholecystectomy.