Patients with nosocomial pneumonia caused by Stenotrophomonas maltophilia often receive inadequate empiric antibiotic therapy, potentially increasing mortality. Knowledge of the risk factors associated with S. maltophilia pneumonia may better guide the selection of empiric antibiotic therapy. Potential risk factors for S. maltophilia pneumonia were retrospectively analyzed for critically ill trauma patients with late-onset gram-negative pneumonia. The effects of S. maltophilia infection and inadequate empiric antibiotic therapy on patient outcomes were also assessed. By multivariate analysis, S. maltophilia pneumonia was found to be associated with cefepime exposure and tracheostomy in patients with a single pneumonia episode and with higher Injury Severity Score and pulmonary contusion in patients with multiple pneumonia episodes. S. maltophilia pneumonia was associated with increased patient morbidity; only inadequate empiric antibiotic therapy was associated with a higher mortality rate. In critically ill trauma patients with late-onset ventilator-associated pneumonia and these risk factors, empiric antibiotic therapy should include agents active against S. maltophilia.