Background: Mount Sinai Beth Israel is a 350-bed, acute-care hospital located on Manhattan’s Lower East Side. In 2014, the hospital had reached a high (9.8 cases per 10,000 patient days ) hospital-onset (HO) C. difficile rate. By 2015, this rate had decreased to 5.6 cases per 10,000 patient days because of compliance with established C.difficile bundle practices performed by nursing and environmental services. Despite these interventions, HO C. difficile events continued to occur. We realized that more had to be done to gain control over our rates. To determine areas for further improvement, infection prevention held an RCA meeting for every positive hospital-onset result. We discovered from these RCAs that many C. difficile tests were ordered without a valid indication. We believed that measures could be taken to ensure that only C. difficile tests with a valid indication would be ordered. Methods: We used the Plan-Do-Study-Act (PDSA) model to look at what changes could be made to reduce our rate and to sustain this reduction. Multidisciplinary meetings of leaders and frontline staff were held to determine why patients were being tested for C. difficile. The following indications were revealed: repeat tests for same patient to “catch” a positive result after the first test was negative; inclusion as part of patient “pan-culturing”; testing patients who had diarrhea after receiving laxatives; and C. difficile cultures for patients who were asymptomatic. Starting in 2016, 3 consecutive interventions were implemented in fairly rapid succession. First, a C. difficile testing algorithm was developed. Second, a C. difficile test order protocol with a “hard stop” to prevent inappropriate indications was placed in the EMR. Last, a multidisciplinary form, called the C. difficile Team Huddle Form, was created for use by all members of the patient’s team. This form gave MDs, RNs, and PCAs a framework to decide together whether the test was indicated for the patient. If the team agreed to test, the ID physician on service was called for approval. Results: These 3 interventions yielded a sustained and statistically significant decrease (P = 0.0007) in the facility-wide hospital-onset C. difficile from a preintervention rate of 5.6 cases per 10,000 patient days in 2015 to 0.4 in 2019. Conclusions: Multidisciplinary use of the C. difficile testing interventions led to further reduction of the hospital-onset C. difficile infection rate. To sustain this rate reduction over time, infection prevention specialists must work with providers and frontline staff on an ongoing basis.