Nosocomial bloodstream infections (NBSI) are associated with increased hospital length of stay (LOS), mortality, and costs. At this writing, no available reports describe the association between injury severity and NBSI among critically ill adult trauma patients. This study aimed to examine the use of the Injury Severity Score (ISS) as a predictor of NBSI among critically ill adult trauma patients. A case-control design was used to compare the mean ISS of 190 critically ill trauma patients equally divided between those with positive test results for NBSI and those with negative results. The mean hospital LOS (34.8 days versus 16.5 days) and the mean intensive care unit LOS (28.1 days versus 13 days) were significantly higher among the patients with NBSI than among the control subjects without such infection (P <.001 and P <.001, respectively). The mean LOS until the diagnosis of NBSI was significantly lower than the total LOS of the control subjects (odds ratio [OR], 0.959; 95% confidence interval [CI], 0.93-0.99). The ISS score and age were found to be independent predictors of NBSI. The findings provide a means for using the ISS score as a predictor of NBSI in the critically ill adult trauma population.