Abstract Background With increasing national focus on reducing inappropriate antimicrobial use, state and national regulatory mandates require hospitals to develop robust antimicrobial stewardship programs (ASP). Methods BJC HealthCare is a 13 hospital healthcare system serving the St. Louis, mid-Missouri, and Southern Illinois region and includes adult and pediatric academic medical centers, as well as community and critical access hospitals. In 2015, BJC system leaders engaged relevant clinical and executive stakeholders at each hospital to champion formation of a multidisciplinary system ASP Council. A comprehensive gap analysis was performed to assess current stewardship resources and activities. BJC system clinical leads facilitated the development of hospital specific leadership support statements, identification of hospital pharmacy and medical leaders, and all mandated educational components. To facilitate tracking, reporting and improvement activities, a robust antimicrobial use data dashboard was created. Each hospital has a dedicated ASP team that is supported by the system clinical leads. Hospital learnings are shared at monthly system ASP meetings allowing for broad dissemination. Results By leveraging system resources, all 13 BJC HealthCare hospitals met all Joint Commission requirements by January 2017. BJC’s model of ASP allows for the development of broad-based stewardship activities including development of education modules for patients and providers, and clinical decision support tools while allowing individual hospitals to implement activities based on local needs and resource availability. Local hospital teams have developed treatment guidelines, targeted antibiotic pharmacy review, “handshake” stewardship models, and allergy testing protocols. Central support of local hospital ASP has resulted in a 7.6% system decrease in tracked antimicrobial use, including a 16.5% reduction in quinolone usage. Additionally, the C. difficilestandardized infection ratio decreased from 1.08 to 0.622 since program initiation. Conclusion Despite significant differences in hospital resources, a system-supported ASP model focused on implementing the CDC core elements can result in significant reductions in antimicrobial use. Disclosures J. Newland, Merck: Grant Investigator, Research grant; Allergan: Grant Investigator, Research grant