Direct oral anticoagulants (DOACs) are increasingly being prescribed for stroke prevention in patients with atrial fibrillation or for treating venous thromboembolism. In this short overview, we provide some guidance on possible differences between available DOACs as well as a comparison with traditional treatments using vitamin K antagonists. In the absence of head-to-head trials comparing different DOACs with each other, this is predominantly based on indirect meta-analysis and observational evidence. Thus, this should be interpreted with caution and considered as expert consensus.