OBJECTIVES: Atrial fibrillation (AF) increases risk of thrombosis (e.g., ischemic stroke (IS), myocardial infarction (MI), systemic embolism (SE)). Conversely, thrombosis prevention increases bleed risk (e.g., gastrointestinal (GI) bleed, intracranial hemorrhage (ICH)). Assessment of the cost-effectiveness of novel anticoagulants (NOACs) relies on comparison of costs and outcomes before and after NOAC availability. However, published AF-specific costs have limited usefulness because they are outdated, limited to Medicare patients, and/or have not captured SE and MI. The objective of this study is to estimate the incremental costs of ‘events’ (IS, MI, SE, ICH, or GI bleed) in patients with AF. METHODS: We conducted a matched (1:4), retrospective cohort study of patients ≥18 years old with incident, AF (ICD-9 427.31) between 2008 and 2010, identified in the Truvan Health MarketScan® Commercial Claims and Medicare Supplemental and Coordination of Benefits Databases. Demographics, baseline healthcare costs, and comorbidities were assessed in the 12 months preceding AF diagnosis.  Cases were defined as having one inpatient admission for an event after AF diagnosis followed by 12 months of continuous enrollment. Controls were AF patients without an event and 12 months of continuous enrollment after a ‘dummy’ event. Multivariate analyses were conducted to assess the incremental cost of each event at 30, 90, and 365 days. RESULTS: We identified 1,788 cases and 7,152 controls. For all events, at all time-points, overall healthcare costs were significantly higher in cases than controls. The mean incremental cost (2012 US$) 30 days after the event was: IS-$20,710; MI- $32,535; SE-$15,754; ICH-$45,242; and GI bleed-$14,823. At all time-points ICH was the most costly while SE and GI bleed were least costly.   CONCLUSIONS: This study is the first to describe AF-specific incremental costs of multiple types of ischemic and bleeding events, prior to NOAC availability. Our results provide tools to assess the value of NOACs.