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This systematic review and meta-analysis aimed to determine the prognostic value of S-100β protein to identify patients with post-concussion symptoms after a mild traumatic brain injury (mTBI). A search strategy was submitted to seven databases from their inception to October 2016. Individual patient data were requested. Cohort studies evaluating the association between S-100β protein level and post-concussion symptoms assessed at least seven days after the mTBI were considered. Outcomes were dichotomized as persistent (≥3 months) or early (≥7 days <3 months). Our search strategy yielded 23,298 citations of which 29 studies including between seven and 223 patients (n = 2505) were included. Post-concussion syndrome (PCS) (16 studies) and neuropsychological symptoms (9 studies) were the most frequently assessed outcomes. The odds of having persistent PCS (odds ratio [OR] 0.62, 95 …