Persons with serious mental illness (SMI) experience one of the largest health disparities in the U.S., with mortality rates two to three times higher than the overall population. Much of this premature death is attributable to cardiovascular disease (CVD), driven by elevated rates of CVD risks (unhealthy diet, physical inactivity, tobacco smoking, obesity, hypertension, diabetes, and dyslipidemia) influenced by interconnected biologic, health behavior, and contextual (e.g., system, policy) factors. Despite the existence of tailored, effective interventions to decrease CVD risk in people with SMI, adoption of these interventions remains limited, contributing to thousands of potentially preventable deaths a year. Our ALACRITY Center was originally created in response to this extraordinary burden of years of life lost and has used cutting-edge transdisciplinary methods to develop and pilot test strategies and conduct methods innovations work to scale practical, effective interventions aimed at reducing CVD risk in this population. In our new application for the Center to Accelerate Translation of Interventions to Decrease Premature Mortality in Persons with Serious Mental Illness, our goal is to continue to build on this foundational work and amplify the Center’s impact through an enhanced focus on health equity, partnership engagement, methods innovations, and building capacity amongst mental health researchers and community partners to improve physical health for persons with SMI. Our uniquely qualified and diverse team will conduct a signature R01 and three R34s to rigorously plan, test, and model implementation strategies addressing all CVD risks in persons with SMI in community settings. We propose: 1) conducting an implementation trial of a behavioral weight loss intervention in two states; 2) piloting a system-level strategy for a CVD risk factor care evidence bundle tailored to people with SMI in primary care; 3) developing and piloting strategies to scale a healthy weight intervention in youth; and 4) systems modeling to inform scaling of evidence-based tobacco cessation treatment in community mental health settings. The Methods Core will grow its transdisciplinary approach incorporating clinical and behavioral intervention research, implementation science, biostatistics, systems science, and health services and policy research to support Center work, and advance methods in: 1) developing a policy implementation measurement framework; 2) identifying implementation strategies’ core components; 3) improving the precision and robustness of implementation trials; and 4) building “hybrid” systems models in implementation science. The Administrative Core will engage partners, building on its well-established Community Advisory Board, lead Center-wide health equity efforts, and bring together all Center activities. The grave disparities in life expectancy and CVD risk burden in persons with SMI call for continued, concentrated, transdisciplinary ...