Tehran University of Medical Sciences Journal of Pharmaceutical Care 2322-4630 13 4 2025 12 31 302 317 Zahra Jahani Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Laleh Mahmoudi Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran Farshad Abedi Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Benyamin Fazli Assistant Professor of Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Mashhad University of Medical Sciences, Mashhad, Iran Amir Hooshang Mohammadpour Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran 2025 09 21 2026 01 25 Background: Post-operative atrial fibrillation (POAF) is a prevalent complication after cardiac surgery, affecting 20-50% of patients and linked to increased morbidity and healthcare costs. Given the central role of oxidative stress in POAF pathogenesis, this review evaluates the efficacy and evidence base of antioxidant drugs for POAF prevention. Methods: A narrative literature review was conducted. We searched PubMed, Scopus, and Web of Science up to April 2025 for studies on antioxidants and POAF prevention. The focus was on randomized controlled trials (RCTs), their meta-analyses, and key mechanistic studies.  Results: Twenty-eight relevant studies were included. Antioxidants, including N-acetylcysteine (NAC), ascorbic acid (vitamin C), L-carnitine, crocin, alpha-lipoic acid, coenzyme Q10, vitamin E, berberine, selenium and melatonin, were evaluated. NAC and vitamin C showed the most consistent benefit, with meta-analyses reporting significant reductions in POAF risk (e.g., pooled RR 0.69, 95% CI 0.52–0.91 for NAC; OR 0.44, 95% CI 0.32–0.61 for vitamin C). Evidence for other agents was less robust, often based on single-center trials or showing contradictory results (e.g., selenium, melatonin). Mechanisms involve ROS scavenging, anti-inflammatory effects, and improved mitochondrial function. Conclusion: Current evidence supports a potential preventive role for specific antioxidants in POAF, particularly NAC and vitamin C. However, significant heterogeneity, contradictory findings for several agents, and a lack of large multicenter RCTs preclude firm clinical recommendations. Antioxidant therapy should currently be considered investigational. Future high-quality trials are needed to establish optimal agents and dosing for clinical practice. https://jpc.tums.ac.ir/index.php/jpc/article/view/898 https://jpc.tums.ac.ir/index.php/jpc/article/download/898/441