BackgroundClostridioides difficile is the most prevalent hospital-onset (HO) infection. There are significant financial and safety impacts associated with HO-C. difficile infections (HO-CDIs) for both patients and health care organizations. The incidence of HO-CDIs at our community hospital within an academic acute health care system was continuously above the national benchmark. MethodsIn response to the high HO-CDI rates at our facility, an interprofessional team selected evidence-based interventions with the goal of reducing HO-CDI incidence rates. Interventions included: diagnostic stewardship, enhanced environmental cleaning, antimicrobial stewardship and education and accountability. ResultsAfter one year, we achieved a 63% reduction in HO-CDI and have sustained a 77% reduction. The infection rate remained below national benchmark for HO-CDI for over 4 years at a rate of 2.80 per 10,000 patient days and a SIR of 0.43 in 2020. DiscussionMultiple evidence-based interventions were successfully implemented over several service lines over a 4-year period through the collaboration of an interprofessional team. The addition of an accountability processes further improved compliance with standards of practice. ConclusionsCollaboration of an interprofessional team led to substantial and sustained reductions in HO-CDI.