Introduction: Post operative nausea and vomiting remains a significant problem in modern anesthetic practice, with an incidence of upto 80% in high risk group patients. Methods: 60 patients were conducted and divided into 2 groups. They received either inj Ondansetron 4mg iv or inj Palonosetron 0.075mg iv which was given 30 min before the end of surgical procedure. Results: At time 0–6 hours, 6–24 hours,24–48 and 48–72 hours overall PONV was less in Palonosetron as compared to ondansetron Conclusion: Palonosetron more significantly reduces the incidence of postoperative nausea and vomiting than Ondansetron.