This epidemiological study analyzed the incidence, risk factors, hospital triage, and outcome of patients with severe traumatic brain injuries (sTBIs) caused by road traffic accidents (RTAs) admitted to hospitals in the Trauma Center West-Netherlands (TCWN) region. Trauma registry data were used to identify TBI in all RTA victims admitted to hospitals in the mid-West region of the Netherlands from 2003 to 2011. Type of head injury and severity were classified using the Abbreviated Injury Scale (AIS). Head injuries with AIS severity scores ≥ 3 were considered sTBI. Ten percent of all 12,503 hospital-admitted RTA victims sustained sTBI, ranging from 5.4% in motorcyclists, 7.4% in motorists, 9.6% in cyclists, and 12.7% in moped riders to 15.1% in pedestrians (p<0.0001). Among RTA victims admitted to hospital, sTBI was most prevalent in pedestrians (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.78-2.86) and moped riders (OR, 1.86; 95% CI, 1.51-2.30). Injury patterns differed between road user groups. Incidence of contusion ranged from 46.6% in cyclists to 74.2% in motorcyclists, whereas basilar and open-skull fractures were least common in motorcyclists (22.6%) and most common in moped riders (51.5%). Hemorrhage incidence ranged from 44.9% (motorists) to 63.6% (pedestrians). Subdural and -arachnoid bleedings were most frequent. Age, Glasgow Coma Scale, and type of hemorrhage were independent prognostic factors for in-hospital mortality after sTBI. In-hospital mortality ranged from 4.2% in moped riders to 14.1% in motorists. Pedestrians have the highest risk to sustain sTBI and, more specifically, intracranial hemorrhage. Hemorrhage and contusion both occur in over 50% of patients with sTBI. Specific brain injury patterns can be distinguished for specific road user groups, and independent prognostic risk factors for sTBI were identified. This knowledge may be used to improve vigilance for particular injuries in specific patient groups and stimulate development of focused diagnostic strategies.