Background: In March 2012, the Veterans’ Health Administration (VHA) published the Guideline for the Prevention of Clostridium difficile infection (CDI) in VHA Inpatient Acute-Care Facilities, with a goal of 30% reduction of cases within 2 years. In March 2011, this facility, along with 31 others, served as a pilot site to develop the guidelines. Methods: The CDI prevention bundle was implemented to prevent new onset CDI cases in the facility with 4 core measures: (1) environmental cleaning (EMS), (2) hand hygiene, (3) contact precautions, and (4) cultural transformation. Education was provided to EMS staff, nursing, and care providers on the CDI case definition, criteria for testing, empiric isolation for patients with diarrhea, hand hygiene, and PPE to control spread. In 2014, antimicrobial stewardship was added, and within 5 years an algorithm for isolation and testing was published. Cases were reviewed weekly using TheraDoc software and were reported monthly to the national VHA Inpatient Evaluation Center (IPEC). Isolation was communicated using a ward roster/isolation list in TheraDoc for all unit champions to consult daily. CDI cases were classified using NHSN definitions for a laboratory-identified (LabID) event, recurrent cases, and community-onset cases. Real-time case review and weekly multidisciplinary case discussions identified opportunities for improved compliance with the core measures. Results: Over an 8-year period, CDI healthcare-onset LabID events decreased by 73%. The cases decreased from 149 to 40 over the 8-year period. The infection rate decreased 70% from 16.19 per 10,000 bed days of care in FY2011 (October 2010) to 4.88 in FY2019. The incidence of community onset infections increased from 75 in FY2011 to a high of 146 in FY2018 for a rate of 8.15 to 18.17. In FY2019, there was a decrease in both LabID events and community-onset cases to lows of 40 and 102, respectively. Inappropriate testing decreased by 84% from 50 in FY2011 to 8 in FY2019. Conclusions: A multidisciplinary team approach that included support from leadership and clinical providers as well as front line staff involvement, daily rounding, and case review by infection preventionists has reduced all CDI cases over an 8-year period using the modified VHA CDI bundle. TheraDoc enabled case review, correct isolation, changes to cleaning practices, and more appropriate lab testing. The antimicrobial stewardship program that includes clinical pharmacists working daily with providers was a strong driver for change.