Background and Purpose- This guideline provides an overview of the evidence on established and emerging risk factors for stroke to provide evidence-based recommendations for the reduction of risk of a first stroke. Methods- Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council Scientific Statement Oversight Committee and the AHA Manuscript Oversight Committee. The writing group used systematic literature reviews (covering the time since the last review was published in 2006 up to April 2009), reference to previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate recommendations using standard AHA criteria (). All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. The guideline underwent extensive peer review by the Stroke Council leadership and the AHA scientific statements oversight committees before consideration and approval by the AHA Science Advisory and Coordinating Committee.(Table is included in full-text article.)(Table is included in full-text article.) Results- Schemes for assessing a persons risk of a first stroke were evaluated. Risk factors or risk markers for a first stroke were classified according to potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented or less well documented). Nonmodifiable risk factors include age, sex, low birth weight, race/ethnicity, and genetic predisposition. Well-documented and modifiable risk factors include hypertension, exposure to cigarette smoke, diabetes, atrial fibrillation and certain other cardiac conditions, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, physical inactivity, and obesity and body fat distribution. Less well-documented or potentially modifiable risk factors include the metabolic syndrome, excessive alcohol consumption, drug abuse, use of oral contraceptives, sleep-disordered breathing, migraine, hyperhomocysteinemia, elevated lipoprotein(a), hypercoagulability, inflammation, and infection. Data on the use of aspirin for primary stroke prevention are reviewed. Conclusion- Extensive evidence identifies a variety of specific factors that increase the risk of a first stroke and that provide strategies for reducing that risk. © 2011 American Heart Association, Inc.