Further details on the Con ict of Interest Policy are available online at http://chestnet.org. Other contributions: We thank Louis Kuritzky, MD, for sharing his perspective as a frontline clinician during the development of our recommendations. Endorsements: This guideline is endorsed by the American Association for Clinical Chemistry, the American College of Clinical Pharmacy, the American Society of Health-System Pharmacists, the American Society of Hematology, and the International Soci- ety of Thrombosis and Hematosis. Additional information: The supplement Tables can be found in the Online Data Supplement at http://chestjournal.chestpubs.org/ content/141/2_suppl/e531S/suppl/DC1. Stroke is a serious complication of AF, but its risk varies considerably across different groups of patients with AF. Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treat- ment based on net clinical bene t for patients with AF at varying levels of stroke risk. Oral anticoag- ulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (eg, CHADS2 score 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach that takes into con- sideration patient values and preferences, bleeding risk, and the presence of non-CHADS2 stroke risk factors. The role of oral anticoagulation for the pre- vention of stroke in patients with AF will evolve as the results of large, ongoing, phase 3 RCTs of new oral anticoagulants are published and as experience with these new agents in clinical practice continues to grow. Acknowledgments Author contributions: As Topic Editor, Dr You oversaw the development of this article, including the data analysis and sub- sequent development of the recommendations contained herein. Dr You: contributed as Topic Editor. Dr Singer: contributed as a panelist. Dr Howard: contributed as a panelist. Dr Lane: contributed as a panelist. 