Background and objectives: Post-operative nausea and vomiting (PONV) is commonly seen in female patients undergoing laparoscopic surgeries under general anaesthesia. Adverse consequences of PONV are patient dissatisfaction, unexpected hospital admission, and delayed recovery. In this randomized double blind prospective study, we compare the efficacy of ondansetron and palonosetron for prevention of PONV. Material and methods: After obtaining ethical clearance and informed consent, 130 female patients undergoing laparoscopic surgery were randomly divided into two groups by sealed envelope method. Group A 8mg ondansetron and group B received 8 mg ondansetron and 0.075 mg palonosetron iv respectively just before induction of general anaesthesia. During the postoperative period occurrence of nausea and vomiting, severity of nausea, rescue antiemetic use and adverse effects were monitored at 0-2 hrs, 2-6 hrs and 6-24 hrs. Results: Number of episodes of vomiting, risk for nausea and vomiting, severity of nausea and need for rescue medication was comparable between the 2 groups during the early post operative period (0- 2 hrs). During 2-6 hrs, the episode of vomiting and use of rescue antiemetic was not different between the two groups but severity of nausea and risk of nausea and vomiting was significantly lower in palonosetron group. During the late post operative period (6-24 hrs), the episodes of vomiting, risk for nausea and vomiting, severity of nausea and need for rescue antiemetics was significantly lower in palonosetron group. Conclusion: Intravenous palonosetron 0.075 mg has a better antiemetic profile when compared to ondansetron 8mg over 24hrs following laparoscopic surgeries under general anaesthesia.