Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF). We sought to determine predictors of OAC initiation in AF patients presenting to the emergency department (ED). Secondary analysis of the RE-LY AF registry which enrolled individuals from 47 countries between 2007 and 2011 who presented to an ED with AF and followed them for 1 year. A total of 4149 patients with AF as their primary diagnosis who were not already taking OAC and had a CHA2DS2-VASc ≥ 1 for men or ≥ 2 for women were included in this analysis. Of these individuals, 26.8% were started on OAC (99.2% vitamin K antagonists) in the ED and 29.8% were using OAC one year later. Factors associated with initiating OAC in the ED included: specialist consultation (relative risk [RR] 1.84, 95%CI 1.44–2.36), rheumatic heart disease (RR 1.60, 95%CI 1.29–1.99), persistence of AF at ED discharge (RR 1.33, 95%CI 1.18–1.50), diabetes mellitus (RR 1.32, 95%CI 1.19–1.47), and hospital admission (RR 1.30, 95%CI 1.14–1.47). Heart failure (RR 0.83, 95%CI 0.74–0.94), antiplatelet agents (RR 0.77, 95%CI 0.69–0.84), and dementia (RR 0.61, 95%CI 0.40–0.94) were inversely associated with OAC initiation. Patients taking OAC when they left the ED were more likely using OAC at 1-year (RR 2.81, 95%CI 2.55–3.09) and had lower rates of death (RR 0.55, 95%CI 0.38–0.79) and stroke (RR 0.59, 95%CI 0.37–0.96). In patients with AF presenting to the ED, prompt initiation of OAC and specialist involvement are associated with a greater use of OAC 1 year later and may result in improved clinical outcomes.