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Optimal red blood cell (RBC) transfusion thresholds in acute brain injury (ABI) are poorly defined.We conducted a retrospective cohort study of adult patients with ABI and moderate anemia (Hb 7–10g/dL) in a neurological intensive care unit (ICU) at an academic medical center between 2008 and 2015. Transfused and non-transfused patients were matched based on age, ABI subtype, pre-transfusion hemoglobin, and ICU length of stay (LOS) at the time of RBC transfusion. Multivariable regression analyses were performed to assess the relationship between RBC transfusion and hospital LOS, hospital mortality, ICU LOS, ICU mortality, and 24h change in sequential organ failure assessment (SOFA) scores.2638 patients met inclusion criteria, with 225 (8.5%) receiving RBC transfusion. Acute ischemic stroke was the most prevalent ABI diagnosis (43.3%) then intracranial hemorrhage (25.6%), subarachnoid hemorrhage (16.5%), and traumatic brain injury (TBI) (14.6%). In multivariable analyses, RBC transfusion was associated with longer hospital and ICU LOS, and higher SOFA scores. Each ABI subtype had similar results, except for TBI which showed no difference in hospital LOS. Mortality was not significantly different.In moderately anemic patients with ABI, RBC transfusion was associated with longer hospital and ICU LOS. Prospective investigations are necessary to further assess these relationships.We studied transfusion in moderately anemic patients with acute brain injury.Red blood cell transfusion was not associated with mortality.Transfusion was associated with increased ICU and hospital length of stay.Findings were largely consistent across acute brain injury subtypes.