Stroke is a leading cause of death and disability in the United States. In the past decade, there have been tremendous strides in the discovery of beneficial approaches to treat and prevent stroke, aided in part by conduct of large-scale clinical trials in StrokeNet. The established Stroke Trials Network has conducted and executed numerous clinical trials with sufficient sample sizes, robust enrollment, timely completion, and rigorous and uniform infrastructure across sites. This application is in response to the recent NINDS request for Regional Coordinating Stroke Centers (RCC) in the NINDS Stroke Trials Network (RFA-NS-23-010). The Chicago Stroke Trials Consortium (CSTC), led by the RCC at University of Chicago (UChicago) has been an integral part of the NIH StrokeNet. In this renewal application, we expand our network to include 12 primary hospitals in the Chicago and Milwaukee metropolitan areas: UChicago Medical Center, Northwestern Memorial Hospital, Rush University Medical Center, University of Illinois at Chicago Hospital, Loyola University Medical Center, John H. Stroger, Jr. Hospital of Cook County, Medical College of Wisconsin’s Froedtert Hospital, Central Dupage Hospital, NorthShore Evanston Hospital, Hines Veterans Affairs Hospital, Lurie Children’s Hospital, and the Shirley Ryan Ability Lab. We have enlisted institutional support including agreements to utilize a federated institutional review board process (central IRB) and master trial agreements to ensure rapid implementation of future trials from each of our participating sites. The RCC aims to combine resources, diverse faculty with stroke expertise, and access to a multi-ethnic population of stroke patients spanning from children to elderly and from acute treatment to rehabilitation. The CSTC will participate in acute stroke, rehabilitation, and prevention trials, and has expertise from investigators in vascular neurology, neurosurgery, neurocritical care, neuroradiology, interventional neuroradiology, neurorehabilitation, pediatric neurology, and emergency medicine. The amassed investigators have backgrounds in all aspects of stroke research and leadership roles in many recently completed and ongoing NIH and industry-sponsored trials. The consortium has a combined geographic referral base encompassing more than 12 million people and has a history of collaboration in clinical and scientific endeavors. Drawing from the vast geographic reach of our hospitals, their resources and investigators, and substantial contributions to StrokeNet during the prior 2 award periods, the CSTC is uniquely qualified to continue to deliver a diverse stroke patient population, provide consolidated multidisciplinary and multi-institutional expertise and leadership for StrokeNet trials, and ensure mentoring for trainees and junior faculty seeking academic careers in stroke.