This study was conducted to determine if clinical features can predict the risk of intracranial injury (ICI) in pediatric closed head trauma. We enrolled 3,806 children under 16 years consecutively referred for acute closed head trauma to the paediatric emergency room of five Italian children’s hospitals. Relevant outcomes were death and diagnosis of ICI. Clinical symptoms and signs were evaluated as possible outcome predictors. Children were also classified into five groups according to their clinical presentation. The association of ICI with signs and symptoms and the appropriateness of the five-group classification in predicting the likelihood of ICI were evaluated by logistic regression analyses. ICI was diagnosed in 22 children; 2 of them died. The risk of fatal and nonfatal ICI was 0.5 and 5.2 per 1,000 children with closed head trauma respectively. Significant associations were found between ICI and loss of consciousness, prolonged headache, persistent drowsiness, abnormal mental status, focal neurological signs, signs of skull fracture in non-frontal areas and signs of basal skull fracture. The five-group classification of children allowed an excellent prediction in terms of likelihood of ICI (ROC area 0.972). Conclusions: Selection of children with closed head trauma based on different combinations of signs and symptoms allows for early identification of subjects at different risk for ICI. In patients with minor head injuries, the absence of loss of consciousness, drowsiness, amnesia, prolonged headache, clinical evidence of basal or non-frontal skull fracture identified 100% of children without lesions. Validation of our results with a larger sample of patients with ICI would be highly desirable.