OBJECTIVES: To estimate the direct costs of maintaining normal sinus rhythm (NSR) in patients with atrial fibrillation (AF) with four antiarrhythmic (AA) drugs (sotalol, amiodarone, flecainide, and propafenone) in the Netherlands (NL). METHODS: A Markov model, with a one month cycle length and a one year treatment duration, was used to estimate expected costs of maintaining NSR. An expert panel of cardiologists was interviewed to collect data on the perceived safety and efficacy of the drugs, resource use (inpatient and outpatient visits, tests and procedures) for recurrence of AF, treatment initiation, monitoring, and side effects. Cost data were obtained principally from the Central Organization for Tariffs in Health Care and the National Association of Pharmacists. Costs were estimated separately by drugs and for patients with and without concomitant structural heart disease (SHD), then weighted by the joint distribution of presence or absence of SHD, specific use of a drug in these two populations, and/or market share of AA drugs. RESULTS: The weighted average annual cost of maintaining NSR in an AF patient was US$2,181.31. Inpatient treatment costs, dominated mainly by costs of symptom recurrence and therapy initiation, ranged from 78% (flecainide) to 92% (sotalol) of total costs. Costs of monitoring and side effects were the highest for amiodarone and sotalol, respectively. Drug costs, ranging from $60 for sotalol to $252 for flecainide, were the minor contributors to the total costs. In patients with SHD, annual costs of maintaining NSR were $2,685 and $2,505 for sotalol and amiodarone, the two most common drugs in the NL, respectively. CONCLUSIONS: The estimated annual cost of maintaining NSR in patients with AF in the NL is as high as US$2,685 per patient. Relatively lower AA drug costs are offset by significant medical treatment costs, particularly for inpatient therapy initiation and recurrence of disease symptoms.