Abstract :The novel oral anticoagulants or direct oral antico- agulants (DOAC) are becoming more common in clinical practice for the prevention of stroke in non-valvular atrial fibrillation (NVAF). The availability of several agents with similar efficacy and safety for stroke prevention in NVAF patients offers more selection, but at the same time requires certain knowledge to make a good choice. This comparative analysis provides an appraisal of the respective clinical trials and highlights much of what remains unknown about four FDA-approved agents: dabigatran, apixaban, rivaroxaban, and edoxaban. It details how the DOACs compare to warfarin and to one another summarizes pharmacologic and pharma- codynamic properties, and drug interactions from the stand point of practical consequences of these findings. Common misconceptions and reservations are addressed. The practical application of this data is intended to help choosing the most appropriate agent for individual NVAF patient.