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Background: Blood transfusion has been associated with worse outcomes in adult trauma patients with traumatic brain injury (TBI). However, the effects in injured children have not been evaluated. We hypothesize that blood transfusion is also associated with worse outcomes in children with TBI., Methods: A retrospective review of the trauma database at two Level I pediatric trauma centers was performed. We reviewed all patients 18 years and younger with TBI, who survived at least 24 hours, from 2002 to 2011. Exclusion criteria include those who underwent craniotomy, thoracotomy, exploratory laparotomy, and any orthopedic procedure., Results: A total of 1,607 children with TBI were included in the study population (mean age, 6.4 [5.7] years; 65% male), 178 of whom received a blood transfusion. Mean Injury Severity Score (ISS) was 16.5 (9.1). Patients who received a transfusion had a higher ISS than those who did not (26.7 vs. 15.3). After controlling for age, sex, ISS, Glasgow Coma Scale (GCS) score on presentation, and mechanism of injury, patients who received a blood transfusion were more likely to be admitted to the intensive care unit (p < 0.0001), less likely to survive to hospital discharge (p = 0.02), more likely to be discharged to a rehabilitation facility (p = 0.01) and be dependent on caretakers at follow-up (p < 0.0001), as well as more likely to develop urinary tract infection (p = 0.02) and bacteremia (p = 0.02) during their hospital stay. These differences in outcomes among those who did and did not receive a blood transfusion began to disappear in patients with a nadir hemoglobin of less than 8.0 g/dL., Conclusion: Pediatric patients sustaining TBI who receive blood transfusion and do not require operative intervention have worse outcomes compared with patients who do not receive transfusion. This includes an increased risk of death. These data suggest that a transfusion trigger of hemoglobin level at 8.0 g/dL in injured children with TBI may be beneficial., Level of Evidence: Epidemiologic study, level III. Therapeutic study, level IV.