We propose to continue our studies of a uniquely informative cohort of greater than 13,559 patients with atrial fibrillation (AF) from Kaiser Medical Care Program of Northern California ("Kaiser"). Our overall goal remains to optimize prevention of stroke in AF by improving selection of patients treated with anticoagulants, and by improving the management of anticoagulation. AF is the most common significant cardiac rhythm disorder. Its frequency increases strikingly with age, reaching a prevalence of nearly 10 percent in those over age 80. AF is also a powerful risk factor for stroke, raising this risk 5-fold. Randomized trials (RCTs) have established that anticoagulation largely removes the stroke risk posed by AF. Nonetheless, warfarin remains a burdensome and risky therapy. There is considerable uncertainty whether warfarin therapy will prove beneficial under real-world conditions. Guidelines call for long-term anticoagulation, and for use of anticoagulants in the elderly. Yet, the RCTs were relatively brief, with a mean follow-up of only 18 months, and few patients greater than or equal to 80 years old were studied. During the 2.7 years of current funding we have established methods to assemble a very large AF cohort, characterize baseline features and warfarin status, and follow for thromboembolic and hemorrhagic events. This has been accomplished efficiently via comprehensive automated clinical and administrative Kaiser databases supplemented by medical chart review. Continued follow-up of our AF cohort will provide unique assessments of both the long-term impact of anticoagulation and the impact of anticoagulation among the oldest patients with AF. Further, we will be able to address other important controversies including the need for anticoagulation in patients greater than or equal to 65 years old without other risk factors for stroke, and the optimal intensity of anticoagulation in older AF patients. In addition, we will address the provocative new finding that estrogen replacement therapy substantially raises the risk of stroke among women with AF. In all, continued study of our cohort will efficiently provide powerful insights into optimizing stroke prevention strategies for the many older Americans with AF.