The direct oral anticoagulants (DOACs) were developed because of the urgent therapeutic need due to the deficits of vitamin K antagonist therapy. The predominant indications in internal medicine are the acute treatment and secondary prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE) as well as stroke prevention in patients with atrial fibrillation. For the acute therapy and secondary prevention of DVT/PE the DOACS were non inferior to low-molecular-weight heparin (LMWH) plus vitamin K antagonists at a significantly reduced rate of severe bleeding complications. Only Rivaroxaban is currently approved for this indication, with Dabigatran, Apixaban and Edoxaban still awaiting approval. For stroke prevention in atrial fibrillation Dabigatran, Rivaroxaban and Apixaban are approved. The efficacy of Dabigatran (150mg bid) and Apixaban (5mg bid) are superior to warfarin, with Rivaroxaban being non-inferior to warfarin for stroke prevention. The rate of bleeding complications with Apixaban and Dabigatran (110mg bid) were significantly lower as with warfarin. The DOACs do represent a major therapeutic advantage in oral anticoagulation therapy of patients for the approved indications.