Background:Postoperative nausea and vomiting (PONV) is a common and distressing complication of surgery under general anesthesia. The present study was conducted to compare palanosetron with ondansetron for postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy under general anaesthesia. Material & Methods:The present randomized double blind study was conducted among 80 patients. Using double blind randomization technique, these patients were divided into Group A (Ondansetron 4 mg fixed dose), Group B (Palonosetron 0.075 mg fixed dose). Any incidence of nausea, retching or vomiting and use of any rescue medication during the first 24 h at time were noted. Side effects were registered. Statistical analyses were done using Statistical Package for Social Science Version 9.0 (SPSS LTD, Chicago, IL and U. S. A). A P < 0.05 was accepted as statistically significant. Results:Mean duration of anesthesia in Group A(32.76mins) and group B (33.76mins) shows non-significant difference. Mean duration of intraoperative fentanyl used in Group A (97.6mins) and group B (96.8 mins) shows non-significant difference. Nausea in Group A patients (25%) and group B (15%) shows significant difference. Retching in Group A patients (5%) and group B (2.5%) shows non-significant difference. Vomiting in Group A patients (20%) and group B (10%) shows non-significant difference. Patients requiring rescue antiemetic in Group A patients (32.5%) and group B (15%) shows significant difference. Incidence of total PONV in Group A patients (50%) and group B (27.5%) shows significant difference. Headache in Group A patients (20%) and group B (7.5%) shows significant difference. Diarrhoea in Group A patients (5%) and group B (2.5%) shows non- significant difference. Dizziness in Group A patients (7.5%) and group B (12.5%) shows significant difference. Conclusion:The present study concluded thatin patients undergoing laproscopic cholecystectomy under general anaesthesia,preoperativelypalanosetron provides a greater anti-nausea impact than preoperativelyondansetron, reduces the need for rescue antiemetics, has a better side effect profile, and has a lower incidence of complete PONV.