PROJECT SUMMARY/ABSTRACT We propose to continue the Stroke Net New England Regional Coordinating Center (NERCC), an integrated team of hospitals in the Greater Boston Area and suburbs, Western Massachusetts, New Hampshire and Vermont that will serve as a top-enrolling site and vibrant contributor to the NINDS Stroke Net Clinical Trials Network. Our group includes most of the major adult academic stroke centers in Massachusetts, New Hampshire and Vermont, and our 30+ hospital New England Tele Stroke referral network will extend our potential recruitment even further. All core hospitals have a proven track record of successful management and performance of clinical trials. In particular, all hospitals have an established research infrastructure that performs ongoing clinical research in stroke neurology with strong collaborations across multiple disciplines. The leadership team composed of Principal investigator Lee H. Schwamm, MD, Deputy PI Aneesh Singhal, MD, Site PIs, Deputy Site PIs, and Co-Investigators bring a diverse and complementary set of skills in managing successful translational clinical research programs, serving as members on trial Steering Committees, and positions of national leadership in their fields. Our team includes seasoned clinical investigators in vascular neurology, emergency medicine, neuroendovascular, neurosurgery, neurointensive care, neuroimaging, stroke rehabilitation, and preclinical basic and translational stroke investigation in both adults and children. Strengths of the NERCC team include 1) close personal and professional ties between multiple investigators and site PIs; 2) a large patient population with geographically diverse hospital settings anchored in a major metropolitan area; 3) talented teams of site investigators with track records of scientific achievement, innovation, and subject recruitment in multicenter trials; 4) robust existing NINDS-funded research and clinical trial management infrastructure at most of the sites; 5) existing clinical research programs, e.g., MGH Neurological Clinical Research Institute, NIH Clinical and Translational Science Award programs serving Boston University and all Harvard hospitals; and 6) leadership roles in the SIREN-NETT, NeuroNEXT, DISCOVERY and MarkVCID trial networks. Overall, the NERCC Team has demonstrated outstanding commitment and performance in the first two Stroke Net cycles, and has the resources, vision, and enthusiasm to continue to develop new translational science and successfully execute the NINDS Stroke Net Phase 1,2 and 3 trials.