Background: Post-operative nausea and vomiting (PONV) is a frequent and distressing complication, with serious implications. As Ramosetron is a newer 5HT3 antagonist, we wanted to evaluate intravenous Ramosetron versus intravenous Ondansetron for prevention of post-operative nausea and vomiting. Methods: This was a hospital based randomized double-blind study conducted in the Department of Anaesthesiology in tertiary care centre from January 2021 to December 2022, among 100 patients who underwent elective laparoscopic surgeries, after obtaining clearance from Institutional Ethics Committee and written informed consent from the study participants. Results: An observation of occurrence of PONV revealed the following : Nausea (PONV score 1) occurred occurred at 0 minutes, 90 minutes, 2 hours in Group R; while vomiting occurred at 4 hours in Group R. In Group O, vomiting (PONV score 2) was observed at 2 hours, 4 hours, 6 hours and 24 hours. Requirement of rescue antiemetic showed a non-significant difference between the two groups with Group R requiring lesser rescue antiemetic. Comparison of various side effects of treatment in two groups signified that difference in occurrence of dizziness was statistically significant between the two groups with dizziness occurring more in Group O. Equal number of patients showed occurrence of headache in both Group R and Group O, and none of the patients experienced drowsiness. Conclusions: Post-operative nausea and vomiting was found to be less in patients receiving intravenous Ramosetron, with less rescue antiemetic requirement as compared to intravenous Ondansetron. Dizziness occurred significantly more in patients who received intravenous ondansetron. Thus, we conclude that intravenous Ramosetron and intravenous Ondansetron have comparable findings in terms of post-operative nausea and vomiting, requirement of rescue antiemetic and requirement of rescue analgesics.