Each year, an estimated 250,000 cases of central line-associated (i.e., central venous catheter-associated) bloodstream infections (BSIs) occur in hospitals in the United States, with an estimated attributable mortality of 12%-25% for each infection. The marginal cost to the health-care system is approximately 25,000 dollars per episode. In 2001, CDC was invited by the Pittsburgh Regional Healthcare Initiative (PRHI) to provide technical assistance for a hospital-based intervention to prevent central line-associated BSIs among intensive care unit (ICU) patients in southwestern Pennsylvania. During a 4-year period, BSI rates among ICU patients declined 68%, from 4.31 to 1.36 per 1,000 central line days. The results suggest that a coordinated, multi-institutional infection-control initiative might be an effective approach to reducing health-care-associated infections.