Converting the health care delivery system into a learning organization is a key strategy for improving health outcomes. Although the collaborative learning organization approach has been successful in neonatal intensive care units and disease-specific collaboratives, there are few examples in general medicine and none in adult medicine that have leveraged the role of hospitalists nationally across multiple institutions to implement improvements. The authors describe the rationale for and early work of the Hospital Medicine Reengineering Network (HOMERuN), a collaborative of hospitals, hospitalists, and multidisciplinary care teams founded in 2011 that seeks to measure, benchmark, and improve the efficiency, quality, and outcomes of care in the hospital and afterwards. Robust and timely evaluation, with learning and refinement of approaches across institutions, should accelerate improvement efforts. The authors review HOMERuN's collaborative model, which focuses on a community-based participatory approach modified to include hospital-based staff as well as the larger community. HOMERuN's initial project is described, focusing on care transition measurement using perspectives from the patient, caregiver, and providers. Next steps and sustainability of the organization are discussed, including benchmarking, collaboration, and effective dissemination of best practices to stakeholders.