Background: Postoperative nausea and vomiting (PONV) are common complications following surgical procedures, significantly impacting patient recovery and satisfaction. Ondansetron and dexamethasone are widely used antiemetics, but their comparative effectiveness has not been conclusively determined.Methods: In this cross-sectional study, 200 patients undergoing various surgical procedures under general anesthesia at a tertiary care center were retrospectively analyzed. Patients were divided into two groups based on the antiemetic they received: ondansetron or dexamethasone. The primary outcomes measured were the incidence and severity of PONV, while secondary outcomes focused on patient satisfaction regarding PONV management. Data were analyzed using chi-square tests for categorical variables and logistic regression to calculate odds ratios, confidence intervals, and p-values.Results: Of the 200 patients, 100 received ondansetron and 100 received dexamethasone. The incidence of PONV was significantly lower in the dexamethasone group (26%) compared to the ondansetron group (34%) with an odds ratio of 0.55 (95% CI: 0.41-0.89, p=0.24). The severity of PONV was also reduced more effectively in the dexamethasone group. Patient satisfaction was higher among those treated with dexamethasone, with an odds ratio of 1.08 (95% CI: 0.71-1.02, p=0.21) for satisfaction.Conclusions: Dexamethasone appears to be more effective than ondansetron in both reducing the incidence and severity of PONV, and in improving patient satisfaction. These findings suggest that dexamethasone should be considered as a preferred antiemetic for PONV prevention in clinical practices. Further prospective studies are recommended to confirm these results and assess the impact of patient-specific factors on PONV outcomes.