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The aim of the study was to systematically review which factor of serum, assessed in traumatic brain injury (TBI), predicts patient’s outcome.Databases were searched for relevant publications between 2005 and January 2013, and those fulfilling the following selection criteria were included: (1) studies conducted from 2005 until February 2013; (2) studies in which factors affecting the outcome after TBI were evaluated; (3) studies that defined TBI as “acute changes in brain function resulting in a strong external force to the head”; (4) studies in which the result was measured by the Glasgow Outcome Score (GCS) or by means of a comparable measure describing the activity limitation and neurological state; (5) studies in which the correlation between the measured factors in the first month after injury and prognosis was addressed; and (6) studies involving patients with moderate and/or severe TBI (GCS<13). All of the papers shortlisted were checked and approved by a specialist and expert in that field. A systematic review and analysis was performed for the prognostic factors assessed in the studies.A total of 71 studies were included, 58 of which were of high quality. Most studies used the GCS at 6 months after injury as the outcome measure, sometimes in combination with other outcome measures. Strong evidence for predicting outcome was found for serum concentration of S100 protein, NSE, MBP, NF-H, GFAP, UCH-L1, blood glucose levels, serum levels of LDH, sodium level, prothrombin time, partial thromboplastin time, platelet count, D-dimer, HSP 70, serum levels of IL-8, number of circulating endothelial progenitor cells (EPCs), and DNA levels in serum.Moderate evidence for predicting outcome was found for high serum MMP9. Strong evidence of no association was found for WBC count and serum cortisol levels, and moderate evidence of no association was found for serum total cholesterol. For other determinants, inconclusive or no evidence or limited evidence was found.S100 protein, NSE, MBP, NF-H, GFAP, UCH-L1, blood glucose levels, serum levels of LDH, sodium level, prothrombin time, partial thromboplastin time, platelet count, D-dimer, HSP 70, serum levels of IL-8, number of circulating EPCs, and DNA levels in serum predicted outcome after TBI. WBC count, serum cortisol levels, total cholesterol, and MMP9 did not have predictive values.