BACKGROUND: Red blood cell transfusion practices vary, and the optimal hemoglobin for patients with traumatic brain injury has not been established. METHODS: A retrospective review of data collected prospectively as part of a randomized, controlled trial involving emergency medical service agencies within the Resuscitation Outcomes Consortium was conducted. In patients with a Glasgow Coma Scale (GCS) score of 8 or less without evidence of shock (defined by a systolic blood pressure [SBP] G 70 or SBP of 70 to 90 with a heart rate Q108), the association of red blood cell transfusion with 28-day survival, adult respiratory distress syndromeYfree survival, Multiple Organ Dysfunction Score (MODs), and 6-month Extended Glasgow Outcome Scale (GOSE) score was modeled usingmultivariable logistic regressionwith robust SEs adjusting for age, sex, injury severity (Injury Severity Score [ISS]), initial GCS score, initial SBP, highest field heart rate, penetrating injury, fluid use, study site, and hemoglobin (Hgb) level. RESULTS: Atotal of 1,158 patients had amean age of 40, 76%weremale, and 98%experienced blunt trauma. The initialmeanGCS scorewas 5, and the initialmean SBPwas 134. Themean headAbbreviated Injury Scale (AIS) scorewas 3.5.Acategorical interaction of red blood cell transfusion stratified by initialHgb showed thatwhen the firstHgbwas greater than 10 g/dL, volume of packed red blood cell was associated with a decreased 28-day survival (odds ratio, 0.83; 95% confidence interval [CI], 0.74-0.93; p < 0.01) and decreased adult respiratory distress syndromeYfree survival (odds ratio, 0.82; 95%CI, 0.74-0.92; p < 0.01). When the initial Hgb was greater than 10, each unit of blood transfused increased the MODs by 0.45 (coefficient 95% CI, 0.19-0.70; p < 0.01). CONCLUSION: In patients with a suspected traumatic brain injury and no evidence of shock, transfusion of red blood cells was associated with worse outcomes when the initial Hgb was greater than 10. Copyright © 2013 Lippincott Williams & Wilkins.