Long-term anticoagulation treatment with warfarin has been associated with a number of limitations in clinical practice and there is a need for more convenient long-term anticoagulation treatment. One of the non-vitamin K oral anticoagulants in development is edoxaban, a factor Xa inhibitor that is administered once daily. The pharmacological properties of edoxaban have various advantages in anticoagulant therapy. Edoxaban quickly reaches peak plasma concentrations in 1.5 h, has a half-life of 10–14 h, has relatively high bioavailability of 62% and exhibits highly selective, competitive, concentration-dependent inhibition of human factor Xa. The plasma concentrations of edoxaban are also closely correlated with suppression of thrombin generation and a range of platelet activation parameters (fragment 1+2, thrombin–antithrombin complex, and β-thromboglobulin), which edoxaban has been shown to rapidly inhibit. The anticoagulant activity of edoxaban is not affected by food intake or ethnicity and a number of drug–drug interaction studies have been performed. Co-administration of edoxaban with strong P-glycoprotein inhibitors, such as dronedarone, quinidine, and verapamil requires edoxaban dose-reduction by 50% to avoid the risk of over-exposure. The exposure of edoxaban may also increase in patients with a body weight ≤60 kg and moderate renal impairment. This meant a dose-reduction strategy in patients at risk of over-exposure was utilized in Phase III clinical studies. In conclusion, the pharmacological properties of edoxaban provide rapid and specific inhibition of factor Xa, which is closely related to plasma concentrations. Given the limitations with long-term warfarin therapy, once-daily edoxaban may provide a convenient long-term alternative for patients.