Background: Laparoscopic cholecystectomy is a standard treatment for cholelithiasis. It is a safe and effective treatment in many cases. General anesthesia has a high incidence for PONV. But anti-emetic drugs can help in preventing PONV. Objectives: To compare the efficacy of ondansetron and metoclopramide in patients undergoing laparoscopic cholecystectomy under general anesthesia. Study Design: Randomized controlled trial. Setting: Department of Anaesthesia, Sheikh Zayed Hospital, Lahore. Period: 6 months i.e. from 15-2-2017 to 15-8-2017. Material & Methods: The patients were divided into two groups. Ondansetron was given to group A patients within 15 minutes of induction, and metoclopramide to group B patients within 15 minutes of induction. Then patients were shifted to the ward after surgery and followed-up for 24 hours for assessment of PONV. All the data was entered and analyzed on SPSS version 20. Results: The mean age of patients in group A was 38.40±12.07 years and in group B was 42.63±11.77 years. The efficacy achieved in 53 were from group A and 39 were from group B Statistically significant difference was found between the study groups i.e. p-value=0.003. Conclusion: Ondansetron showed significantly better efficacy than metoclopramide in preventing PONV after laparoscopic cholecystectomy under general anesthesia.