BACKGROUND: Atrial fibrillation is common among patients with cardiovascular disease and is a frequent complication of the acute coronary syndrome. Data are needed on recent trends in the magnitude, clinical features, treatment, and prognostic impact of preexisting and new-onset atrial fibrillation in patients hospitalized with an acute coronary syndrome. METHODS: The study population consisted of 59,032 patients hospitalized with an acute coronary syndrome at 113 sites in the Global Registry of Acute Coronary Events Study between 2000 and 2007. RESULTS: A total of 4494 participants (7.6%) with acute coronary syndrome reported a history of atrial fibrillation and 3112 participants (5.3%) developed new-onset atrial fibrillation during their hospitalization. Rates of new-onset atrial fibrillation (5.5%-4.5%) and preexisting atrial fibrillation (7.4%-6.7%) declined during the study. Preexisting atrial fibrillation was associated with older age and greater cardiovascular disease burden, whereas new-onset atrial fibrillation was closely related to the severity of the index acute coronary syndrome. Patients with atrial fibrillation were less likely than patients without atrial fibrillation to receive evidence-based therapies and more likely to develop in-hospital complications, including heart failure. Overall hospital death rates in patients with new-onset and preexisting atrial fibrillation were 14.5% and 8.9%, respectively, compared with 1.2% in those without atrial fibrillation. Short-term death rates in patients with atrial fibrillation declined over the study period. CONCLUSIONS: Despite a reduction in the rates of, and mortality from, atrial fibrillation, this arrhythmia exerts a significant adverse effect on survival among patients hospitalized with an acute coronary syndrome. Opportunities exist to improve the identification and treatment of patients with acute coronary syndrome with, or at risk for, atrial fibrillation to reduce the incidence and resultant complications of this dysrhythmia.