Minor head trauma is a common reason for consultation in pediatric emergency departments. In 2009, the Pediatric Emergency Care Applied Research Network (PECARN) published a clinical decision rule for its management. It aimed to help clinicians identify children with a very low risk of developing intracranial lesions, so that unnecessary cranial computed tomography (CCT) scan radiation could be avoided, as such exposure is associated with a rising risk of cancer in this young population. In the meantime, the serum S100β neuroprotein showed encouraging results, with a 30% potential decrease in CCTs for the management of minor head traumas in adults and children. The aim of this study was to determine if the serum S100β neuroprotein, associated with the PECARN clinical decision rule, could safely reduce the use of CCTs. We included children who were examined at the pediatric emergency department for minor head trauma, who underwent a CCT, whose blood samples were analyzed to determine the level of the serum S100β protein. They were managed according to the PECARN clinical decision rule. We afterward assessed the potential decrease in the number of CCTs, according to a modified PECARN clinicobiological decision rule, had we taken into account the result of the blood tests. One hundred nine children were included, and nine of them had clinically important traumatic brain injury. Four of them had a negative S100β value but were classified as high risk of developing intracranial lesion according to the PECARN clinical decision rule. Had we taken into account the modified PECARN clinicobiological decision rule, none of them would have been missed. However, there were 32 true negatives of the rule, allowing a potential decrease in CCTs rated at 29% (95% confidence interval, 21-38). Integrating the serum S100β neuroprotein assessment in the PECARN clinical decision rule could avoid deleterious exposure to CCT radiation, with the condition of using a clinicobiological rule to avoid missing clinically important traumatic brain injuries. Those results have yet to be confirmed relying on a large multicentric study.