Background: The HMO Research Network’s (HMORN) key values center on collaboration and teamwork to improve individual and population health. The HMORN has a renewed interest in forming external partnerships beyond current HMORN members. Minnesota has historically been on the forefront of health reform and innovation. Providers, payers, higher education, and government agencies in Minnesota have worked collectively in the areas of quality improvement and measurement, payment reform, and public health. Building on and extending the success of the HMORN model of research, HealthPartners Institute for Education and Research (the Institute) initiated a regional model of collaborative research in Minnesota. Methods: The Institute hosted discussions with other regional health care organizations in 2010. By the end of 2011, a core group formally launched the new Midwest Research Network (MWRN). Members of the original steering committee represent several research and provider organizations (including the Institute and Essentia Institute for Rural Health); the University of Minnesota CTSI; Minnesota’s Medicare Quality Improvement Organization; and the Institute for Clinical Systems Improvement. The committee drafted a mission statement focused on collaborating “in the development, implementation, and application of research that improves the health outcomes, experience, and affordability of health care for all of the people in our region.” General principles of the network were formalized, and rules for engaging in grants and projects were established. Results: During the first six months in existence, MWRN members jointly submitted three partnership grants focused on primary care decision support tools; patient engagement in quality and cost measures; and testing data sharing protocols. Smaller interest groups have formed around topics in Informatics, Patient Engagement, and Mental Health. The MWRN Mental Health group hopes to define projects that may extend the reach of the national Mental Health Research Network. The new Minnesota Health Information Exchange is also engaged in the MWRN and will be partnering to test using the Exchange to disseminate research findings in the region. Conclusions: The HMORN model of collaborative research can be successfully implemented at a regional level, which may be a valuable source of new external partnerships for the HMORN.