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Objectives: Incidence of postoperative nausea and vomiting (PONV), without active intervention, following laparoscopic cholecystectomy is unacceptably high. We evaluated the effectiveness of intravenous (IV) palonosetron in counteracting PONV during the first 24hrs following laparoscopic cholecystectomy, using ondansetron as the comparator drug. Materials and Methods: In a randomized, controlled, single blind, parallel group trial, single pre-induction IV doses of palonosetron (75mcg) or ondansetron (4mg) were administered to adult patients of either sex undergoing elective laparoscopic cholecystectomy. There were 49 subjects per group. The pre-anesthetic regimen, anesthesia procedure and laparoscopic technique were uniform. The primary effectiveness measure was total number of PONV episodes in the 24 hrs period following end of surgery. The frequencies of individual nausea, retching and vomiting episodes, visual analog scale (VAS) score for nausea at 2, 6 and 24hrs, use of rescue antiemetic (metoclopramide), number of complete responders (no PONV or use of rescue in 24 hrs) and adverse events were secondary measures. Results: There was no statistically significant difference between the groups in primary outcome. Similarly, the frequencies of nausea, retching and vomiting episodes, when considered individually, did not show significant difference. Nausea score was comparable at all time points. With palonosetron, 14 subjects (28.6%) required rescue medication while 13 (26.5%) did so with ondansetron. The number of complete responders was 14 (28.6%) and 16 (32.7%), respectively. Adverse events were few and mild. QTc prolongation was not encountered. Conclusion: Palonosetron is comparable to ondansetron for PONV prophylaxis in elective laparoscopic cholecystectomy when administered as single pre-induction dose. [ABSTRACT FROM AUTHOR]