OBJECTIVES: To perform a cost-effectiveness analysis (CEA) for the use of  dronedarone in patients with atrial fibrillation (AF) in order to prevent hospitalizations due to cardiovascular events or death  (HCED), from the public health care system perspective in Mexico. METHODS:  A CEA was made based on the clinical information from the multicenter, randomized, clinical study ATHENA, where dronedarone was compared to placebo on top of standard treatment in patients with AF. Overall, 2301 patients were randomized to dronedarone, and 2327 to placebo. The primary clinical endpoint was HCED. Only direct medical health care costs were calculated. The health resource utilization was elicited from the ATHENA trial. The unit costs of each event were obtained from the medical literature and/or validated by local experts, whenever information was not available. Most of the cost information is based on IMSS (Social Security) figures, and updated to year 2009 (1€=MX$17.05).  A discount rate of 5% was used. An incremental cost effectiveness analysis was performed complemented by a deterministic sensitivity analysis (DSA) to assess robustness of the model.   RESULTS: Patients randomized to dronedarone experienced 1190 events of HCED (average rate 0.51 [CI 95%: 0.47–0.55]) while patients in the placebo group had 1601 (average rate 0.69 [CI 95%: 0.64–0.74]), or -415 events, 18% less hospitalizations (CI 95%: 12-25%) for the dronedarone group. The average cost per patient in the dronedarone group was €3028 as compared to the placebo group of €2,941, yielding a cost difference of €87.4, and an avoided incremental cost per HCED of €477.00 of dronedarone vs. the placebo group. The DSA shows the analysis is robust. CONCLUSIONS: According to the ATHENA trial, dronedarone is a cost-effective treatment option for the reduction of HCED from the Mexican perspective. Dronedarone’s value could be enhanced if indirect costs averted from the decreased rates of HCED included.