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BACKGROUND: In 2012 the European Society of Cardiology (ESC) published new guidelines on pharmacological stroke prophylaxis in non-valvular atrial fibrillation (AF). The health economics of adhering to these guidelines in clinical practice remains to be elucidated.OBJECTIVE: This paper offers a health economic evaluation of two stroke-prophylactic treatment strategies: complete national adherence to the ESC guidelines on stroke prophylaxis in AF versus stroke-prophylactic treatment prior to 2012 in Denmark.METHODS: A cost-utility analysis was performed to compare two treatment strategies. The first strategy reflected national guideline adherence with the use of non-vitamin K antagonist oral anticoagulants (i.e. dabigatran etexilate), warfarin, and no treatment. The second strategy reflected observed stroke prophylaxis prior to 2012 with the utilization of warfarin, acetylsalicylic acid, and no treatment. A Danish health sector perspective was adopted. A Markov model was designed and populated with information on input parameters from the literature and local cost data reflecting 2014 values. A modeled patient cohort was constructed with a risk profile intended to reflect that of the Danish patient population with AF. The applied outcome was quality-adjusted life-years (QALYs).RESULTS: The incremental cost-effectiveness ratio amounted to 3557 per QALY for the guideline-adherent treatment strategy (GTS) compared with the pre-2012 treatment strategy. This ratio is below a threshold of 25,000 (£20,000) per QALY. Sensitivity analyses revealed that the result was largely robust to changes in input parameters. All analyses found the GTS to be cost effective.CONCLUSIONS: Guideline adherence is a cost-effective treatment strategy compared with the strategy employed prior to 2012 for pharmacological stroke prophylaxis in AF.