Background: Postoperative nausea and vomiting (PONV) remain common complications following gynecological surgeries, often leading to patient discomfort and prolonged recovery. This study aimed to evaluate the impact of dexamethasone in preventing PONV in women undergoing gynecological surgery at a tertiary care hospital. Methods: This was a prospective observational study conducted in the Department of Anaesthesiology, Square Hospital and Bangladesh Medical College Hospital, Dhaka, Bangladesh, from April 2014 to March 2015. This study included 100 women who underwent elective gynecological surgery under general anesthesia. They were randomly allocated into two groups: Group A (n=50) - Patients received intravenous dexamethasone, and Group B (n=50) - Patients received intravenous granisetron. Results: Baseline characteristics were comparable between groups, with a mean age of 44.45 ± 9.74 years in the Dexamethasone group and 44.26 ± 9.89 years in the Granisetron group. The mean BMI was similar (24.7 ± 1.69 vs 24.56 ± 2.27). Adnexectomy was the most common surgery in both groups. Duration of surgery (70.21 ± 19.62 vs 72.11 ± 16.60 min, p = 0.602) and anesthesia (93.22 ± 18.58 vs 95.23 ± 21.94 min, p = 0.622) did not differ significantly. A history of PONV was reported in 4.0% of patients in the Dexamethasone group and 6.0% in the Granisetron group (p = 0.660). Postoperatively, nausea occurred in 14.0% vs 12.0% (p = 0.587), vomiting in 6.0% vs 8.0% (p = 0.750), and metoclopramide use in 6.0% vs 8.0% (p = 0.750), with no significant differences. Side effects were minimal and comparable between groups. Conclusion: Dexamethasone was as effective as granisetron in preventing postoperative nausea and vomiting in women undergoing gynecological surgery, with no significant difference in efficacy or side effects. Both agents appear to be safe options for PONV prophylaxis in this patient population.