Postoperative nausea and vomiting (PONV) has been variously described as the “big little problem” the “nal therapeutic challenge” for anaesthesiology. The commonest cause of morbidity after anaesthesia and surgery are pain and postoperative nausea vomiting 1. To compare the incidences of PONV following laparoscopic cholecyetectomy in different groups of patients receiving ondansetron, palonosetron and Granisetron. 2. To identify the better strategy for prevention of PONV. This is a prospective randomized double blinded clinical study. Both patient and observer were blinded to the group allocation. Allocations to three groups were strictly condential and concealed. One and half year (18 months). Patients undergoing elective laparoscopic cholecystectomy under General Anaesthesia at General Surgery operation theatres of Bankura Sammilani Medical College and Hospital, Bankura The effects of palonosetron, granisetron and ondansetron in preventing PONV (postoperative nausea vomiting) were compared in patients undergoing laparoscopic cholecystectomy and it was found that palonosetron was best and granisetron better in comparison with ondansetron in preventing postoperative nausea and vomiting. Palonosetron provides more effective prophylaxis of early PON (postoperative nausea), late PON (postoperative nausea), and late POV (postoperative vomiting) compared with granisetron and ondansetron. Palonosetron could provide effective prophylactic antiemetic control to prevent PONVafter laparoscopic cholecystectomy surgery under general anesthesia.