The risk of stroke in atrial fibrillation (AF) needs to be assessed in each patient to determine the clinical and cost-effectiveness of thromboprophylaxis, with the aim of appropriate use of antithrombotic therapy. To achieve this, stroke risk factors in AF populations need to be identified and stroke risk stratification models have been devised on the basis of these risk factors. In this article, we firstly provide a systematic review of studies examining the attributable stroke risk of various clinical, demographic and echocardiographic patient characteristics in AF populations. Secondly, we performed a systematic review of published stroke risk stratification models, in terms of the results of the review of stroke risk factors and their ability to accurately discriminate between different levels of stroke risk. Thirdly, we review the health economic evidence relating to the cost-effectiveness of anticoagulation and antiplatelet therapy as thromboprophylaxis in AF patients. The studies included in the systematic review of stroke risk factors identified history of stroke or TIA, increasing age, hypertension and structural heart disease (left-ventricular dysfunction or hypertrophy) to be good predictors of stroke risk in AF patients. The evidence regarding diabetes mellitus, gender and other patient characteristics was less consistent. Three stroke risk stratification models were identified that were able to discriminate between different categories of stroke risk to at least 95% accuracy. Few models had addressed the cumulative nature of risk factors where a combination of risk factors would confer a greater risk than either factor alone. In patients at high risk of stroke, anticoagulation is cost effective, but not for those with a low risk of stroke. With the evidence available for stroke risk factors and the various alternative stroke risk stratification models, a review of these models in terms of the evidence on which they are devised and their performance in representative AF populations is important. The appropriate administration of thromboprophylaxis in AF patients would need to balance the risks and benefits of antithrombotic therapy with its cost-effectiveness.