OBJECTIVES: To compare the incremental cost-effectiveness ratio (ICER) of the reversible direct thrombin inhibitor dabigatran 150mg BID with those of the Xa factor inhibitors rivaroxaban and apixaban from the Mexican public health institution perspective. METHODS: The ICER´s were calculated using a Markov model with a 10-year time horizon for patients over 65 and diagnosed with atrial fibrillation. Each treatment arm started with a cohort of 10,000 patients. The clinical events tracked were incorporated: ischemic stroke, systematic embolism, transient ischemic stroke, hemorrhagic stroke, intracranial hemorrhage, extracranial hemorrhage, acute myocardial infarction, minor bleed and death. Transition probabilities were calculated based on indirect comparisons of published phase III clinical trials. Costs are adapted to the Mexican public health institution perspective. Costs were calculated using published literature, and national costs taken from pharmaceutical companies and public health institutions. Cost-effectiveness was based on the 1GDP per capita threshold established by the National Health Council in Mexico. Costs and outcomes were discounted at a 5% annual-rate. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty of the variables. RESULTS: Dabigatran was found to be dominant when compared with rivaroxaban and apixaban. A reduction on risk for cardiovascular complications was the key advantage of dabigatran. Dabigatran was also more effective when compared with warfarin (69,435 vs. 68,373 life years gained) although more costly (USD$192.76 vs USD$190.73 million dollars). The ICER was USD $1,910.43 per life year which is considered highly cost-effectiveness. The Incremental Cost-Utility Ratio per QALY gained was USD$1,549.00. CONCLUSIONS: The ICER and ICUR of Dabigatran are well below 1GDP (USD$ 10,483.26) per capita versus warfarina. Dabigatran was found to be dominant in comparison with all other treatments. As such, dabigatran can be considered a very cost-effective intervention for the Mexican population over 65 with atrial fibrillation.