OBJECTIVES: The objective of the study was to estimate the direct costs of maintaining normal sinus rhythm (NSR) in patients with atrial fibrillation or flutter (AF/F) with five antiarrhythmic (AA) agents (amiodarone, flecainide, propafenone, quinidine, sotalol). METHODS: A Markov model was used to estimate the expected costs of maintaining NSR in patients with AF/F using AA therapies. Estimates of the resource utilization (inpatient therapy initiation and monitoring, recurrence, and side effects), and efficacy and safety of AA agents were obtained from an expert panel of fifteen cardiologists. Unit costs were estimated from published studies and Medicare and state reimbursement rates. Expected costs for each therapy were estimated for patients with and without structural heart disease (SHD), then weighted by corresponding estimates of prescription frequencies to obtain expected costs for a typical patient. RESULTS: The annual costs of maintaining NSR in patients with and without SHD ranged from $3,984 (quinidine) to $4,749 (amiodarone) and from $2,912 (quinidine) to $3,773 (sotalol) per patient, respectively. For a typical patient, the total annual cost of maintaining NSR was $3,809. Costs of therapy initiation and side effects were estimated to be $ 1,341 and $1,198, respectively; together, these constituted 67% of total treatment cost. Costs of inpatient care represented over 64% of total cost. CONCLUSIONS: The cost of maintaining NSR with available AA therapies is $3,809 for a typical AF/F patient. Costs of inpatient therapy initiation and side effects constitute the majority of the total cost. Total treatment costs are highest for amiodarone and sotalol in patients with and without SHD, respectively.