Although patients with severe multiple injuries may have other reasons for unconsciousness, traumatic brain injury (TBI) in these patients is frequently defined by the Glasgow Coma Scale (GCS). Nevertheless, the diagnostic value of GCS for severe TBI in the multiple-injured patient is unknown. Therefore, we investigated the diagnostic value of GCS to identify severe TBI in multiple-injured patients. The records of 18,002 severely injured adult (ISS >16) patients from the Trauma Register of the German Society for Trauma Surgery were analyzed and initial GCS and Abbreviated Injury Scale (head) (AIS(head)) were recorded. A severe TBI was defined by an AIS(head) ≥ 3. On the other hand, unconsciousness was defined by an initial GCS ≤ 8. By these criteria, 6546 patients (36.3%) were unconscious, and 8746 patients (48.6%) had severe TBI. Nine percent of all cases (n=1643) had a GCS ≤ 8 without severe TBI. Only 56.1% of patients with severe TBI (n=4903) had been unconscious. Decreasing levels of unconsciousness (as defined by GCS) showed consistent rising prevalence of severe TBI (correlation coefficient r=-0.52). Approximately 20% of all multiple-injured patients arriving in the emergency department with an initial GCS of 15 had severe TBI (AIS(head) ≥ 3). The diagnostic value of GCS ≤ 8 for severe TBI in patients with multiple injuries has low sensitivity (56.1%) but higher specificity (82.2%). Our study indicates that the GCS (as defined ≤ 8) in unconsciousness patients with multiple injuries shows only a moderate correlation with the diagnosis of severe TBI. Nevertheless, the main reason for unconsciousness in patients with multiple injuries is TBI, since only 9% of these patients had another reason for unconsciousness. However, due to the poor sensitivity of GCS, we suggest the use of the anatomical scoring system with AIS(head) ≥ 3 to define severe TBI in patients with multiple injuries.