Purpose This article serves as a review of the current literature regarding the role of edoxaban for the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and the treatment of venous thromboembolism (VTE). Summary Until recent years, oral treatment options for both treatment and prevention of VTE and stroke were limited to warfarin. Dabigatran was the first new oral anticoagulant approved in over 50 years followed by rivaroxaban and apixaban. These new oral anticoagulants offer many benefits over warfarin. Edoxaban is the newest member among the oral anticoagulants and exerts its action by direct inhibition of factor Xa. It may offer some advantages in that it is the second Food and Drug Administration-approved once-daily anticoagulant available and does not interact with the cytochrome P450 (CYP450) system. However, there are concerns in patients with AF and preserved renal function (>95 mL/min), as these cohorts experienced a higher incidence of stroke in trials. Conclusion Based on the 3 clinical trials, edoxaban appears to be a safe and effective factor Xa inhibitor in patients with a creatinine clearance of <95 mL/min. It will serve as an alternative anticoagulant for those with a preference for once-daily dosing and/or taking medications that interact with the CYP450 system.