OBJECTIVES: Atrial Fibrillation (AF) is a common cardiac arrhythmia and a significant cause of morbidity and mortality worldwide. As it is necessary to maximize value from the money spent in health care, an economic evaluation was undertaken to compare a new therapy, Dronedarone, in relation to Amiodarone, Sotalol and Propafenone already used in the Greek National Health Service (NHS) setting. METHODS: An international Markov model was locally adapted. The model reflects the management and the progression of AF patients through different health states in the course of their life time, including stroke, post stroke, heart failure (HF), post-HF, acute coronary symptom (ACS) post-ACS and death. Clinical and quality of life data to populate the model were derived from a variety of relevant clinical studies and registries including: ATHENA, AFTER, DIONYSOS, AFFIRM and synthesizing analyses undertaken by academic experts. Resource utilization and cost data were derived by means of a large and representative panel of local experts, who utilized patient data files and data which came from a sample of NHS hospitals. Data refer to the year 2010 and all outcomes were discounted at a rate of 3.5%.  The model is probabilistic to account for uncertainly and mean estimates are reported with corresponding uncertainty intervals. RESULTS: Mean total treatment costs were: Dronedarone: €12,931 (95%UI: 12,065-€12,495); Amiodarone: €8,893 (95%UI: €8,685-€9,100); Sotalol:  €6,185 (95%UI: €5,901-€6,509); Propafenone: €8,433 (95%UI: €8,229-€8,642).  The incremental cost-per-life-year-gained with Dronedarone versus Amiodarone was: €2236 (95%UI: 1897-€2615), versus Sotalol: €2576 (95%UI: €2442-€2822 and versus Propafenone: €2718 (95%UI: €2497-€3395). The incremental cost-per-quality-adjusted-life-year gained with Dronedarone versus Amiodarone was: €3275 (95%UI: 2730-€3838), versus Sotalol: €4319 (95%UI: €4130-€4510) and versus Propafenone: €3138 (95%UI: €2571-€4004). CONCLUSIONS: The newly available treatment Dronedarone appears to be a cost-effective alternative to other already existing therapies, used in the management of Atrial Fibrillation patients in the Greek NHS.