OBJECTIVES: In the ATHENA trial, dronedarone significantly reduced the risk of hospitalizations for cardiovascular (CV) causes or death in patients with atrial fibrillation (AF) and/or atrial flutter (AFL). We evaluated the costs of ATHENA-like trial endpoints among a cohort of US AF/AFL patients without heart failure (HF) who had employer-sponsored Medicare supplemental insurance. METHODS: This retrospective cohort study used claims data from 2004 to 2007 from the MarketScan® databases from Thomson Reuters. Patients were included if they were aged ≥70 years, had evidence of non-transient AF/AFL in 2005 (index diagnosis) and ≥1 CV disease/risk factors but no HF during the 12 months pre-index diagnosis, and had ≥12 months’ continuous enrollment following the first observed hospitalization (index hospitalization) post-index diagnosis. Direct health care costs were calculated for 12 months following the index hospitalization. RESULTS: Overall, 10,200 AF/AFL patients (mean age 79.5 years; 46.8% men) were included; 38.4% had ≥1 rehospitalization for any cause (post index hospitalization). Hospitalization for CV causes occurred in 51.3% of all patients; with a total of 6,436 CV hospitalizations (mean cost $10,908/hospitalization). CV inpatient deaths occurred in 2.6% of patients (mean cost $18,565/death). The most frequent cause of CV hospitalizations was AF/other supraventricular rhythm disorders; the most frequent cause of death during a CV hospitalization was gastrointestinal/intracranial bleeding. Acute/subacute endocarditis was the most expensive cause of a CV hospitalization (mean $81,121/event) and CV surgery was the most expensive cause of CV inpatient death (mean $29,873/death). Non-fatal cardiac arrest was the least expensive cause of a CV hospitalization ($1961/event) and ventricular arrhythmia the least expensive cause of inpatient death during a CV hospitalization ($6146/death). CONCLUSIONS: The costs of ATHENA-like trial endpoints (CV hospitalizations and inpatient death) are high in US AF/AFL patients without HF. Dronedarone may reduce CV hospitalizations and mortality in similar patients and potentially reduce associated costs.