: To compare demographic, injury and hospitalization characteristics and mortality between Isolated and Non-Isolated traumatic brain injury.: A retrospective study based on the Israeli National Trauma Registry of patients hospitalized for traumatic brain injury (TBI) between 2008 and 2016. Isolated TBI was defined as no other anatomic region was having concomitant injury with AIS ≥2. test and multivariate logistic regression analysis were used for data analysis.: Of the 23566-study population, 40.4% were admitted for isolated TBI. Isolated TBI was significantly more frequent in elderly aged ≥65 years, female, Jews, and injuries sustained at home or in residential institution. The Non-isolated TBI was greater in road traffic injuries, particularly among pedestrians and motor cyclists, and in violence injuries. The Non-isolated TBI group had greater injury severity and hospital resource utilization. In-hospital mortality was higher in the patients with Non-isolated TBI [OR: 1.56(95% CI: 1.33-1.83)], particularly in patients with GCS 13-15; elderly aged 65+ years; and patients with concomitant injuries to abdomen, spine or external body regions.: In a patient with TBI, concomitant injuries with AIS ≥2 matter, and awareness of the identified factors has relevance for guiding injury prevention efforts and indeed for potentially improving care and outcome.