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Optimal timing of femur fracture fixation remains controversial. This study examines the association between the timing of femur fracture fixation and outcome in patients with concomitant chest and head injuries.A retrospective review of registry data from a Level I trauma center identified 1362 patients with a femoral shaft fracture over a 12-year period. Patients were categorized into five groups by timing of femur fracture fixation: Group 1, within 24 hours; Group 2, 24 to 48 hours; Group 3, 48 to 120 hours; Group 4, > 120 hours; and Group 5, patients with no operative fixation. Primary outcome measures included morbidity (specifically, pulmonary complications) and mortality. Secondary outcome measures were hospital length of stay, intensive care unit length of stay, and discharge Glasgow Coma Scale score. Subsets of patients were examined including all patients with multiple injuries (Injury Severity Score > 15), chest trauma (Chest Abbreviated Injury Scale score ≥ 2), and head trauma (Head Abbreviated Injury Scale score ≥ 2).Acute respiratory distress syndrome, pneumonia, hospital length of stay, and intensive care unit length of stay were lowest in the group fixed within 24 hours, even in patients with concomitant head or chest trauma. Fixation between 2 and 5 days was associated with a significantly increased incidence of acute respiratory distress syndrome, pneumonia, and fat embolization syndrome in patients with concurrent chest trauma (p < 0.0001). In head-injured patients, discharge Glasgow Coma Scale score was highest in the group fixed within 24 hours. Timing of operative fixation did not affect mortality.Our data show that early femur fracture fixation (< 24 hours) is associated with an improved outcome, even in patients with coexistent head and/or chest trauma. Fixation of femur fractures at 2 to 5 days was associated with a significant increase in pulmonary complications, particularly with concomitant head or chest trauma, and length of stay. Chest and head trauma are not contraindications to early fixation with reamed intramedullary nailing.