Edoxaban is a direct oral anticoagulant (DOAC) and possible alternative to fondaparinux with warfarin in patients with venous thromboembolism (VTE). Edoxaban has been used instead of fondaparinux with warfarin as a first line treatment for pulmonary thromboembolism (PTE) and deep vein thrombosis (DVT) in our clinical pathway since September 2014 due to the VTE insurance reimbursement. We retrospectively recruited 59 patients (edoxaban group: 35 pts, from September 2014 to July 2015, fondaparinux with warfarin group: 24 pts, from April 2011 to July 2015) who had been treated for VTE. Various factors—length of stay (LOS), efficacy and safety outcomes—were compared between the two groups. LOS was significantly shorter in the edoxaban group than in the fondaparinux with warfarin group (10.9 +/– 4.7 days vs. 18.6 +/– 7.3 days, p=0.00014). No significant differences in efficacy outcomes (eg, residual thrombus by CT and D-dimer) or in safety outcomes (eg, bleeding complications and mortality) were observed. Edoxaban is a feasible, safe treatment for VTE compared with fondaparinux with warfarin. Furthermore, the use of edoxaban simplifies treatment and shortens LOS.