Background: Elderly patients with atrial fibrillation (AF) treated with anticoagulants are at higher risk of both ischemic and bleeding events compared to younger patients. Intracranial bleeding (ICH) remains one of the most concerning complications of anticoagulation therapy, and risk is strongly related to age. The ENGAGE AF-TIMI 48 trial showed that both the high (HD) and low dose (LD) regimens of the once daily oral factor Xa inhibitor edoxaban were non-inferior to well-managed warfarin (TTR 68.4%) in preventing stroke and systemic embolic events (SEE) while reducing major bleeding. Methods: 21,105 patients were enrolled in ENGAGE-TIMI 48 trial and stratified into pre-specified age categories: Results: Regardless of treatment, the risk of major bleeding and stroke/SEE increased with age (p Conclusion: The efficacy and safety of edoxaban compared to well-managed warfarin are consistent regardless of age in patients with AF. Due to the higher risk of bleeding with increasing age, the absolute benefits of edoxaban are greater in the elderly.