OBJECTIVES: In large observational studies, eight to 12% of patients with acute coronary syndromes (ACS) have prevalent atrial fibrillation (AF).  However, the determinants of subsequent ACS development in the patient population with incident AF have not been well described. We hypothesized that risk factors present at the onset of AF might identify individuals at increased risk for ACS over the following three years. METHODS: The 5% Medicare database was used to identify 18,445 patients (no ESRD, age 65+) who had new-onset AF in 2006 and no AF or ACS in the year prior.   Medicare claims were used to identify patients hospitalized with any acute myocardial infarction (AMI, ICD-9-CM diagnosis code 410, 410.X, 410.X0, or 410.X1) and unstable angina (code 411). Cumulative incidence was calculated for the competing risks of ACS and death. RESULTS: Patients who had incident AF (n=18,445) in 2006 and no ACS in the previous 12 months had multiple comorbidities.  The most prevalent comorbidities were hypertension (67%), coronary artery disease (33%), diabetes mellitus (26%), dysrhythmia (26%), dyslipidemia (24%), other cardiovascular disease (23%), heart failure (21%), chronic obstructive pulmonary disease (18%), and cerebrovascular accident/TIA (15%).  Overall, 8% of new-onset AF patients experienced ACS within three years.  The cumulative risk of developing ACS was higher in patients with comorbidities.  For example, 6% of patients with either diabetes, HF or CAD developed ACS within one year; this rate increased to 11% by three years.  The risk of developing ACS at three years increased by 5% relative to year one. CONCLUSIONS: Patients with new-onset AF are at risk for atherothrombotic adverse outcomes such as ACS in addition to their recognized increased risk for thromboembolic stroke.   Approximately one out of every 12 patients (8%) with newly diagnosed AF developed ACS within three years; this risk was substantially increased by comorbid diabetes, heart failure, or coronary disease.