Background and Aim: Postoperative nausea and vomiting still occur with unacceptable frequency and the description of it as the ‘Big Little Problem’ encapsulates much of the general perception. The incidence is quite high even after laparoscopic surgeries including gall bladder surgeries. Present study was conducted to assess the level of PONV following laparoscopic cholecystectomy and the effect of dexamethasone and ondansetron, individually on PONV following laparoscopic cholecystectomy. Materials & Methods: The study was conducted at Department of Anesthesia Gujarat Adani Institute of Medical Science, Bhuj, Kutch, Gujarat. 60 patients presenting for elective laparoscopic cholecystectomy were randomised to 3 groups. Group 1 as control, group 2 received dexamethasone and group 3 received ondansetron for PONV prophylaxis. All three groups were evaluated for incidence of post­operative nausea and vomiting. Comparison of the observation among different groups was done and statistically analyzed using Fisher’s exact test and Mannwhitney­U test. Results: The incidence of PONV was 50% in the control group, compared to 12% in the dexamethasone group and 22% in the ondansetron group during the first 24 hours. At 1 hour the total incidence of PONV was 85% in control group, 30% in dexamethasone group and 25% in ondansetron group. At 4 hours the total incidence of PONV was 60% in control group, 5% in dexamethasone group and 15% in ondansetron group. The incidence of PONV at 8 hours was 55% in control group, 10% in dexamethasone group and 40% in ondansetron group. Conclusion: The incidence of PONV following laparoscopic cholecystectomy is high and both dexamethasone and ondansetron effectively reduce the incidence of PONV in these patients.