Edoxaban, a direct factor Xa inhibitor (FXa), is the fourth direct oral anticoagulant (DOAC) approved for clinical use in the treatment of venous thromboembolism (VTE) in Latin America, following global approvals for this indication. Edoxaban features some particular characteristics when compared to the previously approved DOACs. This review summarizes the main properties of edoxaban, the outcomes results of its pivotal global clinical trials and the peculiar clinical features of this compound. This practical guide aims to help Latin America clinicians understand edoxaban, its proper indication and its use for the appropriate patients with VTE.