Introduction:Post–operative Nausea and Vomiting (PONV) is the most common distressing symptom following surgical procedures which can lead to medical complications and impose economic burden on the patients with psychological effects in patients experiencing anxiety about undergoing further surgery. Purpose: The purpose of the study was to compare the efficacy of intravenous palonosetron versus ondansetron in preventing PONV in laparoscopic surgeries. Materials and Methods:A randomized,double–blind interventional study was conducted in the Department of Anaesthesiology,SMS Medical College and Hospital,Jaipur,Rajasthan,India.100 adult patients were divided into two groups of 50 each,randomized to receive 0.075 mg of palonosetron and 4 mg of ondansetron before induction.The occurrence of nausea, vomiting and severity of nausea according to a visual analog scale were observed immediately after the end of surgery at 0–2hrs,2–6hrs,6–12hrs and12–24hrs.Injection metoclopramide was used as a rescue antiemetic.Details of any adverse events were recorded. Results:The incidence of postoperative nausea and overall PONV were lower in Group P than Group O, which was statistically significant (P < 0.05). Conclusion:Palonosetron 0.075 mg IV produced a lower incidence of PONV compared with ondansetron 4 mg IV in patients undergoing laparoscopic surgeries.