The risk for stroke in the patients with atrial fibrillation (AF) was five folds as high as in those without. Long-term effective anticoagulation is crucial in the AF patients with moderate to high risk for stroke. This article highlights the characteristics, advantages and disadvantages of vitamin K antagonists (VKAs) against direct oral anticoagulants (DOACs), and discusses the safety and effectiveness of VKAs for the prevention of stroke in patients with AF as compared with DOACs. The article then provides practical guidance whether to stay on VKAs or switch from VKAs to DOACs.