We propose the creation of “Precision Medicine Initiative New England” (PMI-NE), an enrollment center that encompasses two leading health care provider (HPO) organizations: Partners HealthCare System (PHS) and Boston Medical Center (BMC), the primary teaching hospital of Boston University School of Medicine (BU). We will provide essential geographic diversity in the Northeast Census Region of the US by complementing the Middle Atlantic Division (NJ, NY, and PA; covered in the Columbia and Pittsburgh PMC HPOs) with the New England Division (CT, ME, MA, NH, RI, and VT). Together, PHS and BMC serve a catchment area of 14.4 million people including a large and diverse proportion of the 4.4 million living in the greater Boston area, large portions of the New England population, and a worldwide referral base. Over a five-year period, PHS and BMC delivered outpatient care to 2,253,618 patients with 863,429 (38%) meeting our recruitment target population criteria. Our organizations have a long history of collaboratively producing and using common, open-standards information technology (IT) that leverages the health care system for discovery and has been adopted nationally and internationally. PHS has already implemented brisk recruitment of patients (more than 46,000 to date, 2,200 consented per month) into the PHS Biobank with many key components of PMI including broad consent, linkage to EMR, electronic surveys, and recontact. In large cutting-edge projects, we have successfully engaged participants as partners in research and sustained longitudinal engagement using traditional as well as innovative IT approaches. As such, we have already developed and tested the IT and clinical infrastructures that will be central to achieving PMI milestones and can rapidly adopt procedures developed by the PMI Consortium. We have an extensive, successful track record of collaboration and contributions to large-scale national networks, including the PCORNet Clinical Data Research Network based at Harvard (named “SCiLHS”) in which PHS and BMC-BU collaborate, eMERGE, and many others (see Past Performance). Our team, comprising diverse stakeholders (physicians, researchers, IT leaders, participants) will cohere to enroll 10,000 patients (46% minority) in service of the PMI Cohort Program (PMI-CP). In the sections that follow, we describe our approach to establishing our PMI-NE HPO and our contributions to the PMI Consortium. We describe well-defined milestones and metrics over the 12-month period of performance.