New oral anticoagulants, soon available in clinical practice, will deeply change the management of venous thromboembolism. The main advantage of these drugs is the route of administration. Moreover, among the new oral anticoagulants, rivaroxaban has a better efficacy than enoxaparin to prevent thromboembolic events after major orthopaedic surgery (THR and TKR). In phase III studies, safety profile seems adequate. A new era for prophylaxis of VTE is beginning with the new oral anticoagulants. However, improvement in the management of patients with renal failure, obese patients or elderly is needed considering that these patients have a high thrombotic and/or hemorrhagic risk.