OBJECTIVES: Patients with atrial fibrillation (AF) are at increased risk of stroke. Furthermore, AF-related strokes are associated with greater severity, disability, and mortality than strokes of other etiologies. Management with vitamin K antagonists (VKAs) like warfarin has been an effective and cost-effective strategy. However, their use requires regular monitoring and is associated with a significant risk of bleeding, among other shortcomings. Dabigatran is a novel oral anticoagulant associated with lower stroke and similar major hemorrhage rates compared to warfarin. This study evaluated the cost-effectiveness of dabigatran for stroke prevention in AF patients for the Dutch situation. METHODS: A Markov model was developed using efficacy data extracted from the RE-LY registration study and cost data from Dutch costing studies. The model contained the following health states: AF, stroke or systemic embolism, transient ischemic attack, intracranial hemorrhage, myocardial infarction, pulmonary embolism, extracranial hemorrhage, minor bleeding, and death. The model allowed for new or recurrent events over the lifetime of the patient. Additionally, factors such as subgroup-specific stroke risk, drug discontinuation, and time in therapeutic range (a measure of quality of anticoagulation) were included in the model. Univariate and probabilistic sensitivity analyses were conducted on the base-case incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case analysis, dabigatran-150mg compared to VKA has an incremental cost of €3,057 and a QALY gain of 0.26, corresponding to an ICER of €11,758/QALY. At an informal willingness-to-pay threshold of €50,000/QALY, the probability that dabigatran is cost-effective was approximately 0.93. Sensitivity analysis identified quality of anticoagulation care, drug-specific stroke risk, and stroke cost as having the biggest impact on the ICER. CONCLUSIONS: Dabigatran may be a cost-effective option for AF patients in The Netherlands. However, updated estimates, specifically for anticoagulation care, stroke risk, and stroke cost in The Netherlands, would further improve and reduce uncertainty surrounding the results.