Atrial fibrillation (AF) and stroke are two prevalent health conditions with many shared risk factors. Over the past two decades, non-vitamin K antagonist oral anticoagulants (NOACs) have emerged as important alternatives to vitamin K antagonists, owing to their efficacy, safety profile, and the absence of a need for frequent international normalized ratio monitoring. Introduced as the most recent NOAC, edoxaban has been approved for stroke prevention in non-valvular AF in numerous countries since 2014. The pivotal phase III Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial demonstrated that edoxaban is as efficacious as warfarin in preventing strokes and systemic embolic events. Furthermore, it is linked to reduced rates of major, life-threatening, intracranial, major, or clinically relevant non-major bleeding events and decreased cardiovascular mortality in AF when compared to warfarin. Growing data highlights the utilization of edoxaban in treating AF patients in clinical settings. This article provides an overview of real-world evidence regarding edoxaban's use in preventing stroke and systemic embolic events in AF patients, emphasizing the concerns that physicians factor into their clinical decision-making.