Tehran University of Medical Sciences (TUMS) Academic Journal of Surgery 2423-3218 9 1 2026 10 25 19 33 Alieh Zamani Kiasari Department of Anesthesiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Aida Ghorbanzadeh Department of Anesthesiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Samira Sobhani Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 2026 05 09 Background: Postoperative nausea and vomiting (PONV) is a common and distressing complication after gynecological surgeries, particularly hysteroscopy. This study aimed to determine the effect of oral betahistine on reducing the incidence and severity of PONV after hysteroscopic surgery under general anesthesia. Methods: This double-blind, randomized clinical trial was conducted on 94 candidates for hysteroscopic surgery at Imam Sari Educational Medical Center in 2024. Patients were randomly assigned to two equal groups (n = 47 each). The intervention group received oral betahistine (16 mg three hours and 8 mg two hours before surgery), and the control group received placebo. The incidence and severity of PONV, pain intensity, morphine and ondansetron consumption, and adverse effects were evaluated at 2, 4, 6, 12, 24, and 48 hours postoperatively. Results: The incidence of PONV was significantly lower in the betahistine group than in the placebo group at all time points (32% vs. 68% over the entire period, p < 0.001). The mean nausea severity was also significantly lower in the betahistine group (2.3 ± 1.4 vs. 4.8 ± 2.1, p < 0.001). Morphine and ondansetron consumption during the 48-hour postoperative period were significantly lower in the betahistine group (p < 0.001). No significant difference in adverse effects was observed between the two groups. Older age, higher BMI, and longer anesthesia duration were identified as independent risk factors for PONV. Conclusions: Prophylactic oral betahistine administration before hysteroscopic surgery under general anesthesia appears to be an effective, safe, and cost-effective strategy to reduce the incidence and severity of PONV, decrease the need for rescue antiemetics, and improve the quality of postoperative recovery. https://ajs.tums.ac.ir/index.php/ajs/article/view/344