Introduction: Postoperative nausea and vomiting (PONV) is a common complication of surgery and anaesthesia. PONV have adverse consequences like: prolonged recovery, hospital readmission, delayed ambulation, disruption of surgical sutures, anxiety and increased perception of pain. Aim of this study is to evaluate the role of ondansatron and palonosetron in prevention of postoperative nausea and vomiting in laparoscopic surgeries under general anaesthesia. Material and Methods:Prospective, randomized, comparative study. After approval from the Institutional Ethical Committee, the study was conducted on 60 patients of either sex, aged 20-75 yrs, of ASA grade I and II and scheduled for elective laparoscopic surgeries under general anaesthesia.. Patients were randomly allocated in two groups: Group A – patients who received i.v.ondansetron 4 mg, Group B – patients who received i.v.palonosetron 0.075 mg. Results: Thirty patients received i.v.ondansetron 4 mg grouped as Group A, another thirty patients received i.v.palonosetron 0.075 mg grouped as Group B. The two drugs Palonosetron is better than Ondansetron for prevention of nausea and vomiting as there is decreased incidence of post operative nausea and vomiting is seen with Palonosetron. Conclusion: The concluded in the study Palonosetron is better than Ondansetron for prevention of nausea and vomiting as there is decreased incidence of post operative nausea and vomiting is seen with Palonosetron.