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Preventing healthcare-associated infection (HAI) is a key contributor to enhancing resident safety in nursing homes. In 2013, the U.S. Department of Health and Human Services approved a plan to enhance resident safety by reducing HAIs in nursing homes, with particular emphasis on reducing indwelling catheter use and catheter-associated urinary tract infection (CAUTI). Lessons learned from a recent multimodal Targeted Infection Prevention program in a group of nursing homes as well as a national initiative to prevent CAUTI in over 950 acute care hospitals called “On the CUSP: STOP CAUTI” will now be implemented in nearly 500 nursing homes in all 50 states through a project funded by the Agency for Healthcare Research and Quality (AHRQ). This “AHRQ Safety Program in Long-Term Care: HAIs/CAUTI” will emphasize professional development in catheter utilization, catheter care and maintenance, and antimicrobial stewardship as well as promoting patient safety culture, team building, and leadership engagement. We anticipate that an approach integrating technical and socio-adaptive principles will serve as a model for future initiatives to reduce other infections, multidrug resistant organisms, and noninfectious adverse events among nursing home residents.