ABSTRACT The All of Us Research Program is a landmark longitudinal cohort study that aims to enroll 1 million or more participants reflecting the diversity of the United States and create a unique biomedical data resource that can equitably advance precision medicine and improve health. Since 2016, the All of Us New England Consortium (AoUNE) has contributed to the success of the national program by engaging and enrolling individuals in Eastern Massachusetts through a collaboration of Mass General Brigham (MGB), New England's largest regional health system, and Boston Medical Center (BMC), the largest safety net hospital in the Northeast. In the process, we have designed and implemented robust procedures for staff onboarding and training, site activation, recruitment, internal and external engagement, participant enrollment and retention, data transfer and biospecimen collection. To date, we have enrolled more than 35,000 Core participants of whom more than 73% come from communities underrepresented in biomedical research (UBR) and retained our participant partners (PPs) through both passive (87%) and active ( 40%) retention activities. We have also contributed to the national All of Us program through participation and leadership roles in multiple national committees and task forces responsible for the program's governance, scientific roadmap, and data collection operations. We now propose to leverage this experience to redesign and expand the reach of AoUNE to provide enrollment, engagement, and retention opportunities to additional components of our current consortium and additional geographical regions of New England: Maine, (which has the most rural population and the oldest median age of any U.S. state) and Rhode Island (which includes a range of diverse communities in terms of race/ethnicity and income). To accomplish this, we have formed partnerships with three new regional medical center (RMC) partners: MaineHealth, an integrated health system serving 12 counties in Maine and New Hampshire, and with two Rhode Island RMCs (Lifespan Health System/Rhode Island Hospital and the Care New England Health System, affiliated with Brown University Center for Primary Care and Prevention). These new partners have extensive experience in community engagement and cohort research. Our proposal has three major aims. First, we will expand the AoUNE consortium to include six new sites across Maine and Rhode Island, enhancing UBR participation, including those from rural geography, racial/ethnic minorities, low income, and low education. Second, we will conduct internal and external engagement activities across the full AoUNE with an emphasis on reaching UBR populations and providing bidirectional value. Third, we will engage and fully enroll 19,000 new diverse participant partners over 5 years (75% UBR and 48% from racial/ethnic minority communities by year 5) and actively retain 40% (and 90% through passive retention). We will also facilitate anticipated components of the All of Us Research Program including participant reassessments and pediatric enrollment. These aims represent an important re-design, renewal, and expansion of All of Us New England that will allow us to i) substantially expand our geographic reach for enrollment and engagement; ii) increase our engagement of UBR participant partners, and iii) enhance our contributions to the diversity, scale, and science of the All of Us Research Program.