INTRODUCTION: Atrial fibrillation (AF) increases the risk of ischemic stroke 5-fold and may not only be responsible for as many as 15% of all strokes that occur but also for larger and more disabling strokes than those attributable to other causes which increase the associated costs of care. Anticoagulation with warfarin in the target INR of 2.5 is a major clinical challenge in real-life practice, given that the complex relationship between warfarin dosage and response is readily altered by a variety of factors such as concurrent medications, illnesses, genetic influences, and dietary/lifestyle changes. Consequently, INR values are out of the target range approximately half of the time in real-life studies compared to clinical trial setting. Current anticoagulation therapies are less likely to be cost-effective in routine clinical practice and need improvement. The aim of this review is to discuss the pharmacoeconomic consequences of this management strategy by analysing the optimal treatment option within specific age and risk groups, confirming current guidelines for a health economic perspective and considering the economic impact on health care policy. METHODS: An electronic search of the Medline/PubMed database from 1966 to 2005 was performed to identify articles dealing with all pharmacoeconomic aspects of stroke prevention in atrial fibrillation. The following search terms were used: 'atrial fibrillation', 'stroke', 'cost', 'warfarin'. RESULTS: Treatment with warfarin is cost-effective (versus aspirin or no therapy) in patients with AF at moderate-to-high risk of stroke. The cost-effectiveness of anticoagulation therapy is driven by the achieved risk reduction rather than the potential benefits estimated from clinical trials. Failure to maintain optimal anticoagulation places patients at risk of complications, the management of which is a significant cost driver. CONCLUSION: Improvement could be achieved by optimising physicians and patient's knowledge driven through prevention campaigns by health care policy.