Approximately 795000 people in the United States have a stroke each year, 610000 of whom have had first attacks, resulting in 6.8 million stroke survivors >19 years of Stroke ranks as the fourth-leading cause of death in the Globally, over the past 4 decades, stroke inci- dence rates have fallen by 42% in high-income countries and increased by >100% in low- and middle-income countries.3 Stroke incidence rates in low- and middle-income countries now exceed those in high-income countries.3 Stroke is a leading cause of functional impairment. For patients who are 65 years of age, 6 months after stroke, 26% are dependent in their activities of daily living, and 46% have Abstract The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of stroke among individuals who have not previously experienced a stroke or transient ischemic attack. Evidence- based recommendations are included for the control of risk factors, interventional approaches to atherosclerotic disease of the cervicocephalic circulation, and antithrombotic treatments for preventing thrombotic and thromboembolic stroke. Further recommendations are provided for genetic and pharmacogenetic testing and for the prevention of stroke in a variety of other specific circumstances, including sickle cell disease and patent foramen ovale. (Stroke. 2014;45:3754-3832.) Key Words: AHA Scientific Statements atrial fibrillation diabetes mellitus hyperlipidemias hypertension intracranial aneurysm ischemia prevention and control smoking stroke Guidelines for the Primary Prevention of Stroke A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association The American Academy of Neurology affirms the value of these guidelines as an educational tool for neurologists. 