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Introduction Although guideline-adherent antithrombotic therapy (ATT) for stroke prevention in atrial fibrillation (AF) is associated with lower mortality and thromboembolism, ATT uptake shows geographic variation worldwide. We aimed to assess thromboembolic risk and baseline ATT by geographic region and identify factors associated with prescription of ATT in a large, truly global registry of patients with recently diagnosed AF. Methods and Results Our analysis comprises 15,092 patients newly diagnosed with non-valvular AF at risk for stroke, enrolled in Phase II of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF). Global oral anticoagulation (OAC) use was 79.9%, being highest in Europe (90.1%), followed by Africa/Middle East (87.4%) and Latin America (85.3%), North America (78.3%) and Asia (55.2%). Among OAC users, vitamin K antagonists (VKAs) have been replaced by non-VKA OACs (NOACs) as the more prevalent OAC option in all regions, with highest use in North America (66.5%) and lowest in Asia (50.2%). In Asia, OAC was 80.4% in community hospitals but only 49.8% in university hospitals and 42.6% in specialist offices, and varied from 21.0% in China to 89.7% in Japan (NOACs at 5.8% in China and 83.3% in Japan). Globally, 76.5% of low-risk patients were prescribed ATT (46.1% OAC), whereas 17.7% high-risk patients were not anticoagulated (Europe 8.8%; North America 18.9%; Asia 42.4%). Conclusion Substantial inter- and intra-regional differences in ATT for stroke prevention in AF are evident in this global registry. While guideline-adherent ATT can be further improved, NOACs are the main contributor to high OAC use worldwide., Competing Interests: Conflicts of Interest: M.M. declared no conflict of interest. M.V.H. has received honoraria for presentations and research grants from Boehringer Ingelheim, Bayer HealthCare, Pfizer, GlaxoSmithKline (GSK) and Actelion Pharmaceuticals. K.J.R. is an employee of RTI Health Solutions, an independent non-profit research organization that does work for government agencies and pharmaceutical companies. S.J.D. has received consultancy fees for serving as a steering committee member for Boehringer Ingelheim. He also holds research grants from St Jude Medical. C.S.M. has received honoraria for presentations as well as research grants from BMS, Boehringer Ingelheim, Bayer HealthCare, Pfizer, AstraZeneca and Johnson & Johnson. H.C.D. has received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from the following: Abbott, Allergan, AstraZeneca, Bayer Vital, BMS, Boehringer Ingelheim, CoAxia, Corimmun, Covidien, Daiichi-Sankyo, D-Pharm, Fresenius, GSK, Janssen-Cilag, Johnson & Johnson, Knoll, Lilly, MSD, Medtronic, MindFrame, Neurobiological Technologies, Novartis, Novo-Nordisk, Paion, Parke-Davis, Pfizer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St Jude, Syngis, Talecris, Thrombogenics, WebMD Global, Wyeth and Yamanouchi. Financial support for research projects was provided by AstraZeneca, GSK, Boehringer Ingelheim, Lundbeck, Novartis, Janssen-Cilag, Sanofi-Aventis, Syngis and Talecris. The Department of Neurology at the University Duisburg-Essen received research grants from the German Research Council (DFG), the German Ministry of Education and Research (BMBF), the European Union, the National Institutes of Health (NIH), the Bertelsmann Foundation and the Heinz-Nixdorf Foundation. H.C.D. has no ownership interest and does not own stocks of any pharmaceutical company; within the past year, he served as the editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerznews, Stroke News, as the co-editor of Cephalalgia and was on the editorial board of Lancet Neurology, Stroke, European Neurology and Cerebrovascular Disorders; he chairs the Treatment Guidelines Committee of the German Society of Neurology and has contributed to the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) guidelines for the treatment of atrial fibrillation. J.L.H. is currently conducting research sponsored by Boehringer Ingelheim as a member of the Executive Steering Committee for the GLORIA-AF Registry, and has received consulting fees from Bayer HealthCare, Janssen-Ortho-McNeil, and Pfizer for advisory activities involving the development of anticoagulant drugs. M.P., S.L., K.Z., C.T. and A.E. are employees of Boehringer Ingelheim. G.Y.H.L. has been a consultant for Bayer/Janssen, Astellas, Merck, Sanofi, Bristol-Myers Squibb (BMS)/Pfizer, Biotronik, Medtronic, Portola, Boehringer Ingelheim, Microlife and Daiichi-Sankyo. He has also been a speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo.