BACKGROUND: The central venous catheter (CVC) is a necessary, yet inherently risky, modern medical device. We aimed to carry out a systems-based intervention designed to facilitate the use of maximal sterile barrier precautions and the use of chlorhexidine for skin antisepsis during insertion of CVC. METHODS: All patients in whom a CVC was inserted at a medical-surgical intensive care unit at a university-affiliated public hospital were included in a before-after trial. The standard CVC kit in routine use before the intervention included a small sterile drape (24" by 36") and 10% povidone-iodine for skin antisepsis. We special ordered a customized kit that, instead, included a large sterile drape (41" by 55") and 2% chlorhexidine gluconate in 70% isopropyl alcohol. Both the standard kit in use before the intervention and the customized kit included identical CVCs. Baseline data included the quarterly CVC-associated bloodstream infection (BSI) rates during the 15 months before the intervention. Comparison data included the quarterly CVC-associated BSI rates during the 15 months after we instituted exclusive use of the customized kit. RESULTS: The mean quarterly CVC-associated BSI rate decreased from a baseline of 11.3 per 1000 CVC-days before the intervention to 3.7 per 1000 CVC-days after the intervention (P < .01). Assuming direct costs of at least 10,000 dollars per CVC-associated BSI, we calculated resultant annualized savings to the hospital of approximately 350,000 dollars. CONCLUSION: Infection control interventions that rely on voluntary changes in human behavior, despite the best intentions of us all, are often unsuccessful. We have demonstrated that a systems-based intervention led to a sustained decrease in the CVC-associated BSI rate, thereby resulting in improved patient safety and decreased cost of care.