Objective: To compare the efficacy of aprepitant and dexamethasone versus metoclopramide and dexamethasone combination in prevention of post-operative nausea and vomiting in females undergoing laparoscopic cholecystectomy. Study Design: Prospective Comparative study. Setting: Department of Anesthesia, CMH Lahore. Period: October 2019 to April 2020. Material & Methods: A total of 140 female patients planned for laparoscopic cholecystectomy under general anesthesia, of age ranges from 35-65 years and ASA classification I and II were recruited for the study and were divided into two equal groups. In group A (n=70), patients were given oral aprepitant 80 mg with once sip of water one hour prior to induction and dexamethasone 8 mg upon induction. In group M (n=70), patients were given a placebo one hour prior to induction and intravenous metoclopramide 10 mg and dexamethasone 8 mg upon induction. Results: Age range in this study was from 37 to 65 years with mean age of 46.82 ± 7.29 years. The mean age of patients in group A was 45.73 ± 6.77 years and in group M was 47.91 ± 7.66 years with p-value of 0.076. In our study, significant difference was found between the efficacy of two groups of drugs. The efficacy of aprepitant and dexamethasone was found in 62 (88.57%) patients, while with metoclopramide and dexamethasone, it was found in 51 (72.86%) patients with p-value of 0.031. Conclusion: it is concluded that aprepitant and dexamethasone combination has higher efficacy as compared to metoclorpromide and dexamethasone in prevention of post-operative nausea and vomiting in elective laparoscopic cholecystectomy.