This article describes how a Medicare-funded Quality Improvement Organization collaborated with a hospital association and multiple cross-continuum partners on a statewide effort to reduce hospital readmissions. Interventions included statewide education on quality improvement strategies and community-specific technical assistance on collaboration approaches, data collection and analysis, and selection and implementation of interventions. Fifteen communities, comprising 16 acute care hospitals, 119 nursing homes, 70 home health agencies, and 32 other health care or social service providers, actively participated over a 4.5-year period. Challenges included problems with end-of-life discussions (80.0%), physician engagement (70.0%), staffing (70.0%), and communication between settings (60.0%). Thirty-day all-cause readmission rates in fee-for-service Medicare patients decreased in most hospital service areas across the state (22/24), and the aggregate statewide readmission rate dropped from 15.2/1000 to 12.1/1000, a relative decrease of 20.3% (P < .001). Despite these positive findings, the specific impact of this collaboration could not be determined because of multiple confounding interventions.