The continued progress in eliminating central line–associated bloodstream infections (CLABSIs) in intensive care units (ICUs) stands as one of the patient safety movement's major successes. The initial efforts to prevent CLABSI in the ICU at Johns Hopkins Hospital, championed by Dr. Peter Pronovost, were subsequently replicated in the landmark Keystone ICU project in Michigan. This study describes the results of an AHRQ-funded effort to extend the Keystone ICU approach nationwide, attempting to prevent infections in more than 1000 ICUs in 44 states. The initiative, which combined the well-publicized infection control checklist with interventions to enhance safety culture (such as the comprehensive unit-based safety program) and continuous data measurement and feedback, achieved a reduction in CLABSI rates of more than 40%. This remarkable series of interventions exemplifies the value of using a sociotechnical approach to improving safety and has likely saved thousands of lives.