Problem Developing a national pragmatic clinical trial infrastructure is central to understanding the effectiveness of interventions applied under usual conditions and where people receive health care. To address this challenge, three Florida universities—the University of Florida Clinical and Translational Science Institute, Florida State University (with its community-based distributive medical education model), and the University of Miami—created (2010–2013) a statewide consortium, the OneFlorida Clinical Research Consortium, to support the conduct of pragmatic clinical trials and provide mentored research experiences for medical and graduate students in real-world practice settings. Approach OneFlorida has four programs, which report to a steering committee with membership from each partner, community members, and the state Medicaid agency and Department of Health to ensure shared governance. The Clinical Research Program provides support to conduct research in the network and uses champions to engage community clinicians. The Citizen Scientist Program has community members who provide input on health topics of importance to them, study design, recruitment and retention strategies, and the interpretation of findings. The Data Trust Program contains electronic health record and health care claims data for 10.6 million Floridians. The Minority Education Program, in collaboration with three historically black colleges and universities, offers minority junior faculty mentoring in pragmatic clinical trials and implementation science. Outcomes OneFlorida has implemented 27 studies with diverse patient populations and in diverse community practice settings. Next Steps To identify evidence-based best practices from the clinical trials conducted in the network, foster their implementation, and expand research training opportunities.