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We sought to determine the effect of a femoral shaft fracture, and its treatment by early intramedullary nailing, on the neurologic outcome of patients with multiple injuries with a concomitant head injury. Retrospective, case-control design using a prospectively gathered trauma data base. We identified 46 patients with multiple injuries (mean Injury Severity Score [ISS] = 33.2) with closed head injuries (mean Glasgow Coma Scale [GCS] score = 7.8) and femur fractures, and matched as controls 99 patients with multiple injuries with head injuries but without femur fractures for age, sex, mechanism of injury, ISS (mean ISS = 34.0), and GCS (mean GCS score = 8.0). Follow-up parameters examined included early mortality, length of hospital or intensive-care unit stay, neuropsychological testing, and level of neurologic disability. There were no significant differences in the demographics or injury parameters between the study and control groups. There were no significant differences between the two groups in terms of early mortality (study group, 28%; control group, 27%; p = not significant), length of hospital/intensive-care unit stay (study group, 17.5/6.9 days; control group, 18.0/6.3 days; p = not significant), level of neurologic disability, or results of cognitive testing. Our study suggests that a femoral fracture in a patient with a concomitant head injury does not increase mortality or neurologic disability, and supports the continued early intramedullary nailing of femoral fractures for these patients.