In a prospective 30-month study of nosocomial infections in a pediatric ICU (PICU), the incidence, sites, and causes of infection were determined. Factors associated with increased risk of infection were investigated. In 1,388 patients who remained in the PICU for a minimum of 72 h, 116 infections occurred (6.1 infections/100 admissions). Primary bacteremias comprised 38% of PICU infections and lower respiratory infections comprised 15%. The remaining infections were divided equally among GI, skin, eye, upper respiratory, postoperative wounds, and other sites. Coagulase-negative staphylococci, Pseudomonas aeruginosa, and Staphylococcus aureus were the most prevalent pathogens. Surgical patients had similar rates of infection to medical patients. Patients in the first 2 yr of life, particularly those between 7 and 30 days of age, had the highest rate of infection. Onset of infection was more common after the first week in the PICU with 11% of patients staying 14 to 20 days, 27% of patients staying 21 to 27 days, 48% of patients staying 28 to 34 days, and 52% of patients staying more than 35 days before the onset of infection. The risk of nosocomial infection increases with arterial and central line use, prolonged intubation, ventilation, intracranial pressure monitoring, and paralysis.