Novel oral anticoagulants have the potential to improve stroke prevention in patients who have atrial fibrillation and an elevated risk of stroke by overcoming several limitations of warfarin, such as the need for regular monitoring and dose adjustment, and the existence of multiple drug interactions and dietary restrictions. In recently completed phase III trials in patients with non-valvular atrial fibrillation, common findings for dabigatran, rivaroxaban, and apixaban compared with warfarin included: risk reductions for stroke and systemic embolism, significantly fewer hemorrhagic strokes and intracranial hemorrhages, and reductions in mortality, although different trends were seen in several endpoints. However, the trials had important differences in terms of design, populations studied, and statistical analysis that preclude comparison between trials and should be considered when interpreting findings. In this article, data for novel anticoagulants are reviewed and some potential practical implications are highlighted. (C) 2013 Elsevier Inc. All rights reserved.