To determine whether blood transfusion influences infection after trauma, we analyzed data on 5366 consecutive patients hospitalized for more than 2 days at eight hospitals over a 2-year period. The incidence of infection was significantly related to the mechanism of injury: penetrating injuries, 8.9%; blunt injuries, 12.9%; and low falls, 21.4%. Stepwise logistic regression analyses of infection using the variables age, sex, respiration rate in the emergency department, Glasgow Coma Scale in the emergency department, Injury Severity Score, shock (systolic blood pressure < 90 mm Hg on admission to the emergency department), and log of total amount of blood transfused during hospitalization showed that amount of blood received and Injury Severity Score were the only two variables that were significant predictors of infection across groups. Even when patients were stratified by Injury Severity Score, the infection rate increased significantly with increases in numbers of units of blood. Blood transfusion in the injured patients is an important independent statistical predictor of infection. Its contribution cannot be attributed to age, sex, or the underlying mechanism of severity of injury.