Background and Aims: PostOperative Nausea and Vomitting (PONV) Continues to be a highly undesirable outcome of anaesthesia and SX. We compared the efficacy of Palanosetron, Ondansetron an Metoclopramide in the control of PONV. Methods: A total of 60 Patients were randomly allocated to three groups, Group (P): received intravenous Palanosetron 0.25mg, Group (O): received intravenou Ondansetron 4mg, Group (M): received intravenous Metoclopramide 10mg. Incidents of Early (0- 2 Hours) and Late Post-Operative (2- 24 hours) Nausea and Vomiting were assessed. Statistical analysis were performed using Chi- square and Fisher ‘f’ probability test. Results: Incidence of Early Post operative nausea (0-2 hours) in Group (P) was 0% (0/20) Compared to Group (O) and Group (M) which were 5% (1/ 20) and 0% (0/20) respectively. Incidence of late post-operative (2 -24 hours) Nausea in Group (P) was 5% (1/20), Group (O) was 20% (4/20) and Group (M) 10% (2/20) respectively. There is no significant difference in the anti nausea efficacy of Palanosetron compared to ondansetron and metoclopramide. The incidence of early post-operative (0-2  hours) vomiting in Group (P) was 0% (0/20), Group (O) 10% (2/20) and Group (M) 5% (1/ 20). Incidence of Post operative (2-24 hours) vomiting in group (P) 5%(1/20), Group (O) 15 (3/20), Group (M) 15% (3/20). Comparing overall incidence of vomiting showed that the antiemetic efficacy of Palanosetron is the same as Ondansetron and Metoclopramide for Post Operative emisis Conclusion: Prophylactic administration of Palonosetron, Ondansetron and Metoclopramide for PONV, there was no significant difference in the anti-nausea and anti-emetic efficacy of Palonosetron compared to Ondrasetron and Metoclopramide. The magnitude of effect against PONV appears to be similar to that of other established drugs.