Elevated systemic levels of S-100B are proposed as a potential indicator of brain damage in identifying high-risk patients after mild head trauma (MHT). Although incidence of alcohol intoxication is high in these patients, the influence of alcohol intoxication on S-100B levels is unclear. Therefore, the aim of our study was to investigate serum concentrations of S-100B in intoxicated (group 1) and sober (group 2) patients after MHT in comparison with those of mild (group 3) or severely intoxicated (group 4) individuals without trauma. S-100B was significantly increased in MHT patients exhibiting posttraumatic lesions in initial cranial computed tomography scan. Alcohol intoxication did not elevate S-100B levels in group 3 or 4 subjects. Our data indicate for the first time that alcohol intoxication does not influence the diagnostic value of S-100B measurements in patients after MHT.