Healthcare-associated infections are common, costly, and often lethal. Although there is growing pressure to reduce these infections, one project thus far has unprecedented collaboration among many groups at every level of health care. After this project produced a 66% reduction in central catheter-associated bloodstream infections and a median central catheter-associated bloodstream infection rate of zero across >100 intensive care units in Michigan, the Agency for Healthcare Research and Quality awarded a grant to spread this project to ten additional states. A program, called On the CUSP: Stop BSI, was formulated from the Michigan project, and additional funding from the Agency for Healthcare Research and Quality and private philanthropy has positioned the program for implementation state by state across the United States. Furthermore, the program is being implemented throughout Spain and England and is undergoing pilot testing in several hospitals in Peru. The model in this program balances the tension between being scientifically rigorous and feasible. The three main components of the model include translating evidence into practice at the bedside to prevent central catheter-associated bloodstream infections, improving culture and teamwork, and having a data collection system to monitor central catheter-associated bloodstream infections and other variables. If successful, this program will be the first national quality improvement program in the United States with quantifiable and measurable goals.