The Innovation in Medical Evidence and Development Surveillance (IMEDS) Network is a collaborative effort between the Reagan-Udall Foundation for the Food and Drug Administration (the Operations Center), the Harvard Pilgrim Health Care Institute (the Analytic Center), and nine selected Network Partners (U.S. regional or national health insurers (CVS Healthspire Payor & Life Sciences LLC, Harvard Pilgrim Health Care, Carelon Research, Inc., HealthPartners Institute, Humana Healthcare Research, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Health System, Vanderbilt University Medical Center, and the University of Massachusetts Chan Medical School Division of Health Systems Science), contributing administrative claims and electronic health record data. The IMEDS network provides real-world healthcare data on large, diverse patient populations, facilitating efficient analyses of medical product safety and effectiveness evaluations, leveraging tools developed by the FDA’s Sentinel Initiative. Between 2000 and 2023, 32.8 million historical members contributing to IMEDS had at least one day of medical and drug coverage, over 105.3 million had at least one year of continuous enrollment, and over 91,000 had a cumulative (continuous) enrollment of at least one year. Network Partners provide data to the Analytic Center in summary form via distributed query. Results are aggregated and shared with partners. IMEDS can be used to support activities including utilization studies, natural history studies, active surveillance programs, post-market requirement or commitment studies, and Risk Evaluation and Mitigation Strategy assessments. Stakeholders who leverage the IMEDS Network benefit from its large, national sample, scientific expertise, and experience leveraging the FDA Sentinel tools to conduct pharmacoepidemiologic activities.