The Health Care Systems Research Network was established in 1992 by the leadership of four research groups embedded in large integrated delivery systems that provide both health care and insurance coverage. Stemming from committed leadership, investigator goodwill, and trusting relationships, the HCSRN has grown to 20 organizations that provide health care and financing to over 32 million people. Participating members share a common purpose: to improve the health of their populations by producing and using knowledge in the public domain and generating collaborative partnerships locally and nationally. Through evolving rules of engagement and a healthy culture of collaboration, the HCSRN is a desired partner for addressing the issues important to our communities. Local and national health policy and funding organizations include HCSRN in planning and prioritizing research needs as well as health care improvement initiatives. HCSRN investigators assemble “special interest groups” which function as incubators for new project ideas and may focus on specific health issues (obesity, cancer) and/or designated populations (child and adolescent health; older adults). Interest groups function both proactively, generating new investigator-initiated projects and reactively, in that they are well-positioned to respond to relevant funding opportunities that arise. To support efficient multi-site projects, research administrators and IRB professionals also convene standing work groups under the auspices of the HCSRN. In these work groups, common templates, tools, and resources are developed to assist protection of research participants and ease the administrative burdens associated with grant development and contracting. Such supportive structures help ensure a rapid and predictable experience by researchers, collaborators, and funders. More than a dozen federally-funded networks within the HCSRN continue to produce an ever expanding portfolio and platform for increasingly complex research. The portfolio includes multi-site condition-specific networks studying mental health, cancer, addiction, and diabetes, as well as population-focused networks studying aging. In each case, these multi-site networks generate dozens of sub-projects, publications, and policy-relevant findings, examples of which will be discussed in this session. Local and national elements of the HCSRN architecture and infrastructure are openly shared to enrich the public commons. Examples include the Virtual Data Warehouse, data query capabilities, streamlined IRB review mechanisms, and governance. The HCSRN's principles and processes have also been applied by members to create local and regional partnerships such as the Midwest Research Network, and have helped shape collaboration between health systems and their local public health agencies. Collectively, the HCSRN is producing learning communities to improve population health and well-being on a national scale.