The sampling of S100B protein has been proposed as a screening tool to identify patients with a low risk of post-traumatic intracranial hemorrhage. Its performance for patients on antiplatelet agents or anticoagulants is still debatable. This exploratory study evaluates the diagnostic accuracy of S100B concentrations, measured within 3 h of head trauma, to rule out intracranial hemorrhage in adults on antiplatelet or anticoagulant therapy. This prospective study enrolled adult patients presenting for head trauma within the last 3 h and under antiplatelets or anticoagulants. We hypothesized that a S100B concentration under 0,100 µg.L