Background: Post-operative nausea and vomiting is very much prevalent and unpleasant complaints with laparoscopic surgeries that leads to numerous emergencies so antiemetic prophylaxis reduced complications associated with nausea and vomiting. Aim and Objectives: To compare an efficacy of ondansetron & dexamethasone singly as well as a combination of both dexamethasone & ondansetron in the patients for those who undergoes laparoscopic surgeries and have a requirement of rescue anti-emetics. Methods: Sample size of the study was 150 patients (50 patients per group) which was between the age group of 20 years to 50 years of ASA I, II for those who chiefly requires a general anesthesia for laparoscopic surgeries in an arbitrary clinical trial. Therefore, 150 patients was divided into 3 group of 50 each of name Ondensetron group (O), Dexamethsone group (D)and OD group and respective drugs was administered 10 minutes before induction, and post-operative patients were evaluated at time interval of 0 to 6 hours (early vomiting category), 6 to 24 hours (delayed vomiting) to check the degree of nausea, vomiting along with the requirements of antiemetic drug. Results: Nausea was the bottom-most in Combination Group OD (considered as 6%) when compared to Ondansetron Group O (considered as 20%) & Dexamethasone Group D (considered as 12%). For vomiting incidence, results were opposite. It was less in OD Group (i.e. 4% only) when compared to O Group (i.e. 12%) & D Group (i.e. 16%). The requirement for antiemetic drug in the above-mentioned groups of O, D and OD was 26, 20 and 6 respectively. Last but not the least, incidence of vomiting & failure in prophylaxis was observed and analyzed in D Group during initial to 6 hours of duration. Also requirement was more for antivomiting drug of post-operation within 6 to 24 hours observed in O Group compare to OD Group. Conclusion: Combination therapy of ondansetron (Group O) & dexamethasone (Group D) shows adequate control of PONV with delayed PONV which was being better controlled than early PONV (as and when compared to ondansetron & dexamethasone one singly). The need of adjunct antiemetics was emphatic reduced in initial 24 hours of duration.