For more than 5 decades, the only available treatment for the prevention of atrial fibrillation (AF)-related stroke were the vitamin K antagonists. Recently, novel oral anticoagulants (NOAC) have been approved for the prevention of AF-related stroke. In the present article, the cost effectiveness of AF-related stroke-prevention strategies is reviewed. The emphasis on NOACs aims to provide an overview of their impact on health economics based on the published cost-effectiveness analyses. The available evidence suggests that the balance from the efficacy and safety point of view makes the treatment with the NOACs a cost-effective alternative to warfarin. Thus, the NOACs offer efficacy, safety and convenience, as well as cost effectiveness, for stroke prevention in AF.