Background: Comparison of the effect of injection ondansetron and palonosetron intravenously on haemodynamic parameters and post operative nausea and vomiting. Materials & methods: A total of 120 patients aged between 18-60 years scheduled for emergency and elective minor surgeries were selected randomly. Patients were divided into two groups: GROUP O –Ondansetron group – 4- 8 mg, and GROUP P – Palonosetron group -0.0075 mg . All the results were recorded in Microsoft excel sheet and were subjected to statistical analysis using SPSS software. Results: Mean age of the patients of the Group O and Group P was 31.5 years and 30.1 years respectively. Mean height among the patients of the Group O and group P was 160.8 cm and 162.7 cm respectively. Mean weight among the patients of the Group O and group P was 69.7 Kg and 71.3 Kg respectively. Both the groups were comparable in terms of age and anthropometric variables. Incidence of postoperative nausea and vomiting was significantly higher among Group O in comparison to group P. While comparing the hemodynamic response in between the two study groups at different time intervals, non-significant results were obtained. Conclusion: Palonosetron is more effective than ondansetron in patients undergoing surgery under spinal anesthesia. However, considering the small sample size and homogenous nature of surgery and anesthesia, the authors believe that further studies with larger sample size need to be undertaken.