OBJECTIVES: Although atrial fibrillation/flutter (AF) is a risk factor for cardiovascular (CV) disease, its morbidity/mortality burden is uncertain. This retrospective cohort study examined CV hospitalization/mortality rates and associated costs among AF patients in the real-world setting. METHODS: The US MarketScan® database was used to identify adults with AF (≥1 AF hospital discharge or ≥2 non-diagnostic outpatient AF claims) and ≥18 months’ continuous enrollment data [≥12 months and ≥6 months’ immediately before and after the first qualifying (index) AF diagnosis] between January 2003 and September 2007. AF was classified as newly-diagnosed (ND) or pre-existing (PRE) based on AF diagnoses in the first 12 months. CV hospitalization and mortality were assessed post-index diagnosis during a mean follow-up period of 20 months.RESULTS: Of 184,155 AF patients identified (mean 73 years, 55% men), 119,486 had PRE and 64,669 had ND disease; common comorbidities included hypertension (60%), heart failure (31%), and diabetes (23%). During post-index follow-up, 80,523 PRE patients (67%) vs. 51,240 ND patients (79%) were hospitalized. Admissions for CV causes were similarly frequent in patients with PRE and ND disease (mean 0.30 vs. 0.33 events/patient, respectively) and incurred similar costs per event for the two groups (mean US$11,898 vs. $12,257, respectively). Causes of CV admission (by DRG) in the overall cohort included cardiac arrhythmia (23%), myocardial infarction (3.8%), syncope (3.2%) and ‘other/unspecified’ (66%). Admissions with an AF diagnosis were more frequent among patients with ND than PRE disease (mean 0.99 vs 0.61 events/patient), but hospital costs for the two groups were similar (mean US$12,059 vs. $11,984, respectively). In total, 2990 (2.5%) PRE patients and 1409 (2.2%) ND patients died in hospital, with most deaths occurring during admission with an AF diagnosis (58% in both groups). CONCLUSIONS: AF is accompanied by a high level of CV hospitalization with associated cost burden and mortality.