Sepsis is a major cause of morbidity and mortality in patients with trauma. To elucidate factors that might lead to infection, we studied the epidemiologic characteristics of nosocomial infections in our patient population with trauma. During a 3.5-year period, 2496 patients were entered into our hospital trauma registry and cross-matched with hospital infection control surveillance information. Two hundred twenty-nine patients with trauma and nosocomial infections were identified (9.2%), a figure that was nearly twice the nosocomial infection rate for the general hospital population. The majority of those infected were either orthopedic (51%), general surgical (25%), or neurosurgical (13%) patients. The most common sites of first infection were urinary tract (61%) or respiratory system (14%). Patients developing nosocomial infections were significantly older and had a higher Injury Severity Score than those who did not. Injury site was related to risk of infection with injuries of the spine, chest, and extremity showing the most significant relationship. The length of stay as well as hospital charges were significantly related to the occurrence of infectious complications. By determining the patient with trauma at risk for infection, treatment strategies can be designed to minimize septic complications.