Clostridium difficile infection (CDI) is a major health threat that disproportionately impacts hospitalized patients. CDI rates are monitored and reported to CMS as part of the Hospital-Acquired Condition (HAC) Reduction Program. Boca Raton Regional Hospital has developed a comprehensive quality improvement initiative which has reduced hospital-acquired CDI rates by 55% in less than a year. This session will focus on CDI reduction through multiple initiatives including clinical decision support to guide ordering patterns, staff education to raise awareness, laboratory testing techniques to reduce false positive rates, and supporting environmental services to prevent transmission. These initiatives can be applied in a variety of clinical settings and should result in significant improvements in iatrogenic CDI rates as well as better performance related to CMS value-based purchasing.