Introduction: Laparoscopic surgeries are associated with an appreciably high rate of post operative nausea and vomiting (PONV). This study was designed to compare the effectiveness of Granisetron with that of Palonosetron for prevention of PONV after laparoscopic surgery. Methods: In a randomized, prospective study, 60 adult patients of both sexes received Granisetron 2.5mg and Palonosetron 75mcg intravenously at the end of surgery. Perioperative anaesthetic care was standardized in all patients. Patients were then observed 24 hours after administration of the study drug. Results: A complete response (defined as no PONV and no need for another rescue antiemetic) was achieved in 75% of the patients given Granisetron and 86% of the patients given Palonosetron with (P<0.05%). No significant difference observed in the recovery time from anesthesia between the two drugs and slight difference in the adverse events were observe d between the two groups. Conclusion: This study concludes that the prophylactic intravenous administration of Palonosetron is more effective drug than Granisetron for controlling postoperative nausea and vomiting with less incidence of side effects.