OBJECTIVES: Patients with atrial fibrillation (AF) are often chronically treated with anticoagulant or antiplatelet drugs for stroke prevention and are especially vulnerable to bleeding. The objective of this retrospective database analysis was to use administrative claims data from a large, national US health care organization to examine the incremental costs of bleeding events in patients with AF. METHODS: Administrative claims data were used to identify patients with AF and bleeding events from January 1, 2002 - December 31, 2005 with continuous enrollment for 1 year prior to AF diagnosis. Patients were stratified into 3 sub-cohorts: intracranial hemorrhaging (ICH), major bleeds and minor bleeds. To assess incremental costs, patients with bleeding were matched on age, gender, region, and month of identification to a cohort of patients with AF and no evidence of bleeding. Multivariate analyses were used to estimate the independent incremental cost attributed to bleeding. RESULTS: A total of 127,135 subjects were identified with AF, 39.1% of whom had bleeding events.  After applying criteria for continuous enrollment and age (≥18 years), a total of 11,266 patients that had evidence of bleeding were identified (1.8% ICH, 10.8% major bleeds and 87.4% minor bleeds).  Compared to matched controls, patients with ICH or major bleed incurred significantly more costs over the 1-year follow up period.  Mean adjusted incremental total costs over the 1-year follow-up period were $258,968 in subjects with ICH and $88,775 in subjects with major bleeds.  Patients with minor bleeds did not incur additional costs compared to controls. CONCLUSIONS: Major bleeding associated with AF is associated with significant costs over and above that of AF alone.  New strategies that further reduce the risk of bleeding among patients with AF could reduce the cost of their care.