Background: Despite clear evidence in critical care that blood transfusion has an adverse impact on outcome, neurosurgical textbooks still recommend transfusion of patients with traumatic brain injury (TBI) to a hematocrit (HCT) of 30%. There is little empirical evidence to support this practice. The current study addresses transfusion requirements in TBI in terms of neurologic outcome. Methods: Retrospective record review of patients with severe TBI. Outcome measures were Glasgow Coma Scale score (GCS), Glasgow Outcome Score (GOS), and Ranchos Los Amigos Score (RLA) at hospital discharge (D/C); and GOS and Functional Independence Measures at follow-up. Association of outcomes with the number of days the HCT < 30% and lowest measured HCT were evaluated. Results: In all, 169 patients reviewed; 150 with D/C outcome data and 72 with long-term follow-up data. Univariate analysis showed that lowest measured HCT was associated with lower D/C GCS, D/C GOS, and RLA scores. Linear regression showed that more days with HCT < 30% were associated with improved neurologic outcomes measured by GOS (R-2 = 0.424, p < 0.001), GCS (R-2 = 0.381, p < 0.001) and RLA (R-2 = 0.392,p < 0.001) scores on D/C. Both transfusion and lowest measured HCT were significantly associated with all lower outcome scores on D/C. Additional factors with adverse impact on outcome were head Abbreviated Injury Score (AIS), Injury Severity Score, hyperglycemia, and hypotension. Long-term outcomes were only significantly associated with head AIS. Conclusions: Patients with severe TBI should not have a different transfusion threshold than other critical care patients. Prospective studies are needed to evaluate the effects of anemia in TBI.