PROJECT SUMMARY/ABSTRACT The “Deep South,” including Alabama, Mississippi, and Louisiana, has the highest rates of obesity, diabetes, and hypertension in the nation. As a result, life expectancy in the Deep South is substantially lower than other regions, and this discrepancy is even greater for Black Americans. The mission of the Deep South Center to Reduce Disparities in Chronic Diseases (P50MD017338) is to promote health equity and reduce the burden of cardiometabolic diseases across the Deep South. The Center focuses on the prevention, treatment, and management of cardiometabolic diseases among Black Americans and low-income populations who suffer disproportionately from these conditions in our tri-state region. The Center is unified thematically through the application of the precision public health approach across the care continuum to achieve health equity, defined as “providing the right intervention to the right population at the right time”. This approach acknowledges the importance of context, culture, individual beliefs, and preferences as well as the need for multi-level and multi-domain interventions. The Center brings together a trans-disciplinary team of investigators from 4 institutions in 3 contiguous states (the University of Alabama at Birmingham, Tuskegee University, Louisiana’s Pennington Biomedical Research Center, and the University of Mississippi Medical Center) as well as regional non-academic partners to extend cardiometabolic research into real-world community and clinical settings. To accomplish its mission, the Center currently includes 3 cores (Administrative Core, Investigator Development Core, and Community Engagement Core) and 3 R01-level research projects, all of which focus on community- or clinic-based interventions for cardiometabolic diseases across the care continuum. This competitive revision builds on the Center’s current work to expand its reach with the addition of four interrelated pilot intervention trials evaluating novel therapeutic interventions for the prevention and management of cardiometabolic diseases among Black Americans. These projects are led by four productive and promising junior investigators committed to health equity research, which further supports the Center’s objectives to grow the number of health equity researchers in the region. Given the significant health disparities in cardiometabolic diseases evident in the Deep South coupled with the infrastructure and collaborations provided by the Center for these new investigators, this competitive revision will further expand the impact of these regional efforts to improve health equity for cardiometabolic outcomes.