Background: Postoperative nausea and vomiting (PONV) is considered most unpleasant experience by the patients in postoperative period. In particular, following laparoscopic procedures the incidence of PONV is very high. The present study is aimed to assess the magnitude of PONV after laparoscopic cholecystectomy and to compare the relative effectiveness of two drug Ondansetr Dexamethasone Subjects and Methods: Ninety adult patient of either sex in the age group of 20 to 50 years of ASA I or II were randomly divided into one of the two groups of forty-five each. Group A patients received 4 mg of ondansetron intravenously towards end of surgery. Group B patients received 8 mg of Dexamethasone injection at the time of induction of anaesthesia. Postoperatively, the patients were assessed for episodes of nausea, vomiting and need for rescue antiemetic at intervals of 0–1, 1-2, 2-4, 4-8, 8-12, 12-24 hours. Results: The incidence of PONV up to 4 hours after surgery was 6 and 9 in Group A and Group B respectively (p>0.05). Thereafter during 4 to 12 hours after surgery, the incidence of PONV was 12 and 4 respectively in Group A and Group B (p<0.05). About 38% female patients had PONV compared  to 20% male patient in-group A. Also 27% female patients had PONV compared to 18% male patient in-group B. Conclusion: Prophylactic Ondansetron in a dose of 4 mg given near the end of surgery and prophylactic Dexamethasone in a dose of 8 mg given at the time of induction is highly effective in reducing the incidence of PONV for 4 hours and 8 hours respectively after surgery. Compared to male population female sex seems to be an independ nt risk factor for PONV.