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To determine whether low levels of S100B in serum can predict normal computed tomography (CT) findings after minor head injury (MHI) in adults.Not applicable.Systematic evidence-based review of the peer-reviewed literature with meta-analytical interpretation.Not applicable.We identified 12 eligible articles that specifically studied adult MHI patients with S100B and cranial CT scans in the acute phase after injury, comprising a total of 2466 separate patients. Individual negative predictive values of 90% to 100% were found for the ability of a negative (under cutoff) S100B level to predict a normal CT scan. A total of 6 patients included in the studies had low S100B levels and positive CT scans (0.26%) and only 1 of these patients (0.04%) had a clinically relevant CT finding. The pooled negative predictive value for all studies was more than 99% (95% CI 98%–100%), with an average prevalence for any CT finding at 8%. The studies are consistently classed as level 2 and level 3 grades of evidence, suggesting a grade B recommendation.Low serum S100B levels accurately predict normal CT findings after MHI in adults. S100B sampling should be considered in MHI patients with no focal neurological deficit, an absence of significant extracerebral injury, should be taken within 3 hours of injury, and the cutoff for omitting CT set at less than 0.10 μg/L. Care givers should also be aware of other clinical factors predictive of intracranial complications after MHI.