Deaths directly due to infection increased from 2% to 4% of the study population in the later period (P = .02). In addition, in each study period, the risk of death was significantly greater for infants who experienced an infection (RR, 1.8; 95% CI, 1.3-2.5 and RR, 1.8; 95% CI, 1.3-2.7 in the earlier and later period, respectively). Despite the greater number of infections in the later period, the attributable risk of mortality (9% and 13%, respectively) did not change (P = .09). In a proportional hazard model using the entire sample in which the risk of death was evaluated with respect to infection during hospitalization, study period, birth weight, corticosteroid exposure, and duration of device use, only lower birth weight (RR, 1.005 per gram; 95% CI, 1.004-1.006) and corticosteroid exposure (RR, 0.4; 95% CI, 0.2-0.7) significantly influenced the risk of death. Duration of central vascular access or mechanical ventilation was of borderline significance (RR, 0.99 per day; 95% CI, 0.98-1.0 for both variables). In separate proportional hazard models in which the risk of death was analyzed with respect to the source of infection (treated as categorical variables: bloodstream, respiratory tract, etc) or the type of organism (treated as categorical variables: gram-negative, gram-positive, or yeast), along with birth weight and device use, neither the source of infection nor the type of organism influenced the risk of death.