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Background: A blood-based biomarker that accurately reflects neuronal injury in acute ischemic stroke could be an easily accessible and cost-effective complement to clinical and radiological evaluation. Here, we investigate whether plasma levels of the novel biomarker brain-derived tau (BD-tau) reflect cerebral infarct volumes and whether BD-tau can improve clinical outcome prediction., Methods: The present study included 713 consecutive cases from two different hospital-based cohorts, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) and SAHLSIS phase 2 (SAHLSIS2). Acute stroke severity was determined by the Scandinavian Stroke Scale converted to the National Institutes of Health stroke scale (NIHSS) in SAHLSIS and by the NIHSS in SAHLSIS2. All participants were assessed for functional outcome 3 months after stroke by the modified Rankin Scale, and 254 participants in SAHLSIS had quantitative neuroimaging available., Findings: Plasma BD-tau concentrations and cerebral infarct volumes were highly correlated (ρ 0.72, p < 0.001). BD-tau improved the prognostic accuracy of suffering an unfavorable outcome over age and stroke severity in the whole cohort. However, the gain in predictive power was dependent on stroke severity and infarct location. The largest improvement was observed for mild ischemic strokes (NIHSS <5; area under the curve [AUC] = 0.73 for age + NIHSS versus AUC = 0.84 with addition of BD-tau; DeLong p 0.02), posterior circulation stroke (AUC = 0.75 vs. AUC = 0.84; DeLong p 0.06) and more specifically for infarcts in the brainstem/cerebellum (AUC = 0.74 vs. 0.87; DeLong p 0.009)., Conclusion: Plasma BD-tau can provide information on the extent of acute neuronal damage in ischemic stroke and adds prognostic value for outcome, especially for mild and posterior circulation strokes., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)