Edoxaban is the most recently approved factor Xa inhibitor within the class of direct oral anticoagulants (DOACs). Like other DOACs, edoxaban was approved by the US Food and Drug Administration for treatment of venous thromboembolism and prevention of stroke in patients with nonvalvular atrial fibrillation. Similar to other DOACs, edoxaban has fewer drug-drug interactions than warfarin and does not require routine laboratory monitoring. Unlike other DOACs, edoxaban has yet to be approved for secondary or postoperative venous thromboembolism thromboprophylaxis. Currently no antidote for edoxaban is available. To optimally prescribe agents in the DOAC class, it is critical that providers 1) understand how the agents compare; and 2) identify specific settings in which one agent may be preferred over another.