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To determine whether a multifaceted systems intervention would eliminate catheter-related bloodstream infections (CR-BSIs).Prospective cohort study in a surgical intensive care unit (ICU) with a concurrent control ICU.The Johns Hopkins Hospital.All patients with a central venous catheter in the ICU.To eliminate CR-BSIs, a quality improvement team implemented five interventions: educating the staff; creating a catheter insertion cart; asking providers daily whether catheters could be removed; implementing a checklist to ensure adherence to evidence-based guidelines for preventing CR-BSIs; and empowering nurses to stop the catheter insertion procedure if a violation of the guidelines was observed.The primary outcome variable was the rate of CR-BSIs per 1,000 catheter days from January 1, 1998, through December 31, 2002. Secondary outcome variables included adherence to evidence-based infection control guidelines during catheter insertion.Before the intervention, we found that physicians followed infection control guidelines during 62% of the procedures. During the intervention time period, the CR-BSI rate in the study ICU decreased from 11.3/1,000 catheter days in the first quarter of 1998 to 0/1,000 catheter days in the fourth quarter of 2002. The CR-BSI rate in the control ICU was 5.7/1,000 catheter days in the first quarter of 1998 and 1.6/1,000 catheter days in the fourth quarter of 2002 (p = .56). We estimate that these interventions may have prevented 43 CR-BSIs, eight deaths, and $1,945,922 in additional costs per year in the study ICU.Multifaceted interventions that helped to ensure adherence with evidence-based infection control guidelines nearly eliminated CR-BSIs in our surgical ICU.