Efforts to reduce infections acquired during a hospital stay through improvements in the quality of care have had measurable results in many hospital settings. In pediatric intensive care units, the right quality interventions can save lives and money. We found that improving practices of hand hygiene, oral care, and central-line catheter care reduced hospital-acquired infections and improved mortality rates among children admitted to a large pediatric intensive care unit in 2007-09. In addition, on average patients admitted after the quality interventions were fully implemented spent 2.3 fewer days in the hospital, their hospitalization cost $12,136 less, and mortality was 2.3 percentage points lower, compared to patients admitted before the interventions. The projected annual cost savings for the single pediatric intensive care unit studied was approximately $12 million. Given the modest expenses incurred for these improvements-which mainly consisted of posters for an educational campaign, a training "fair," roughly $21 per day for oral care kits, about $0.60 per day for chlorhexidine antiseptic patches, and hand sanitizers attached to the walls outside patients' rooms-this represents a significant return on investment. Used on a larger scale, these quality improvements could save lives and reduce costs for patients, hospitals, and payers around the country, provided that sustained efforts ensure compliance with new protocols and achieve long-lasting changes.