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Background: Evidence-based best practices are available for the reduction and prevention of Clostridioides difficile infection (CDI). Often, these practices are not consistently followed in many inpatient care settings. A learning collaborative model resulted in a cost neutral, rapid, sustainable, statistically significant reduction in CDI events across an 88-hospital campus system without requiring hospitals to standardize laboratory methods, increase spending or increase staffing. Methods: In March 2018, a healthcare system with 88 critical access and community hospital campuses across 29 states participated in a harms-reduction learning collaborative. The collaborative format included educational webinars, gap analyses, action plans, and coaching calls facilitated by subject matter experts (SMEs). A collaborative cohort of 11 hospitals (55% rural*) was identified as having significant opportunity for improvement. These facilities participated in 3 monthly coaching calls. The coaching calls supported peer-to-peer sharing of practices and discussions of challenges and successes, and educational materials and presentations were provided by SMEs in pharmacy and infection prevention. Results: Statistically significant changes for the 88-hospital system as a whole: (1) 2018 compared to 2017: P < .001 (statistically significant); (2) 1H2018 compared to 2H2018 (before-and-after collaborative): P = .001; (3) 2019 compared to 2018: P < .001 (statistically significant). Statistically significant changes for the collaborative cohort: (1) 2018 compared to 2017: P < .001; (2) 1H2018 compared to 2H2018 (before-and-after collaborative): P = .002; and (3) 2019 compared to 2018: P < .001. We used 2-proportion, 2-tailed z-test for our analysis. Conclusions: Utilizing a learning collaborative model that included webinars, gap analyses, and interactive coaching calls, a cohort of 11 hospitals was able to induce rapid improvements to adherence of evidence-based practices resulting in a rapid, sustained, statistically significant improvement for both the cohort hospitals and the healthcare system.*2018 American community survey, US Census.Funding: NoneDisclosures: None

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