Atrial Fibrillation (AF) has a worldwide increasing incidence and prevalence, putting patients at risk for atrial thrombus formation and consecutive thromboembolic events. Morbidity and mortality have become a significant global public health care burden. Thus, there is increasing need for safe and effective medical prophylaxis of thromboembolic events. Edoxaban is the fourth approved non-vitamin K oral anticoagulant (NOAC) that has been introduced into the market for the prophylaxis of stroke or systemic embolism in non valvulär AF patients after dabigatran, rivaroxaban, and apixaban. The pivotal phase III clinical trial evaluating safety and efficacy of edoxaban included more than 21,000 patients. Areas covered: The aim of this expert opinion drug safety review is to introduce edoxaban as a compound, to discuss its development, and its pharmacologic properties. Furthermore, efficacy and safety data of edoxaban - with emphasis on a comparison to oral anticoagulation with warfarin and the other currently available NOACs - are discussed. Ongoing studies that further evaluate edoxaban in special patient populations and disease entities are summarized. Expert opinion: Concerning safety and efficacy, medical compliance, adherence and concomitant diseases like renal impairment are of utmost importance in daily clinical practice, why in the expert opinion part of this review emphasis is put on that issue.