Acute brain injury is a critical health challenge with substantial mortality and morbidity. While anemia is common in these patients and may worsen outcomes, the optimal red blood cell transfusion strategy remains controversial.

We conducted a meta-analysis with trial sequential analysis of randomized controlled trials (RCTs) comparing liberal versus restrictive transfusion strategies in patients with acute brain injury.

Pubmed, Embase, and the Cochrane Library databases were searched through December 15, 2024, for RCT comparing liberal (hemoglobin threshold 9−10 g/dL) versus restrictive (hemoglobin threshold 7−8 g/dL) transfusion strategies in adults with acute brain injury. The primary outcome was an unfavorable neurological outcome.

Six RCTs involving 2599 patients were included. There was no significant difference in unfavorable neurological outcomes between liberal and restrictive strategies (risk ratio [RR], 0.97; 95% confidence interval [CI], 0.83–1.14; p = 0.70). Similarly, no differences were observed in overall mortality (RR, 0.98; 95% CI, 0.85–1.12; p = 0.75), hospital mortality (RR, 1.02; 95% CI, 0.79–1.31; p = 0.89), or intensive care unit (ICU) mortality (RR, 0.74; 95% CI, 0.28–1.91; p = 0.53). Although transfusion reaction was non-significantly more frequent with liberal transfusion (RR, 1.13; 95% CI, 0.35–3.58; p = 0.84).

In patients with acute brain injury, a restrictive transfusion strategy was not associated with worse neurological outcomes or higher mortality compared to a liberal strategy.

Maintaining hemoglobin levels above 7–8 g/dL may be effective for patients with acute brain injury, potentially reducing unnecessary transfusions and associated risks.

registered on PROSPERO under number CRD42025639745.