OBJECTIVE Traumatic brain injury (TBI)-the "silent epidemic"-contributes to worldwide death and disability more than any other traumatic insult. Yet, TBI incidence and distribution across regions and socioeconomic divides remain unknown. In an effort to promote advocacy, understanding, and targeted intervention, the authors sought to quantify the case burden of TBI across World Health Organization (WHO) regions and World Bank (WB) income groups. METHODS Open-source epidemiological data on road traffic injuries (RTIs) were used to model the incidence of TBI using literature-derived ratios. First, a systematic review on the proportion of RTIs resulting in TBI was conducted, and a meta-analysis of study-derived proportions was performed. Next, a separate systematic review identified primary source studies describing mechanisms of injury contributing to TBI, and an additional meta-analysis yielded a proportion of TBI that is secondary to the mechanism of RTI. Then, the incidence of RTI as published by the Global Burden of Disease Study 2015 was applied to these two ratios to generate the incidence and estimated case volume of TBI for each WHO region and WB income group. RESULTS Relevant articles and registries were identified via systematic review; study quality was higher in the high-income countries (HICs) than in the low- and middle-income countries (LMICs). Sixty-nine million (95% CI 64-74 million) individuals worldwide are estimated to sustain a TBI each year. The proportion of TBIs resulting from road traffic collisions was greatest in Africa and Southeast Asia (both 56%) and lowest in North America (25%). The incidence of RTI was similar in Southeast Asia (1.5% of the population per year) and Europe (1.2%). The overall incidence of TBI per 100,000 people was greatest in North America (1299 cases, 95% CI 650-1947) and Europe (1012 cases, 95% CI 911-1113) and least in Africa (801 cases, 95% CI 732-871) and the Eastern Mediterranean (897 cases, 95% CI 771-1023). The LMICs experience nearly 3 times more cases of TBI proportionally than HICs. CONCLUSIONS Sixty-nine million (95% CI 64-74 million) individuals are estimated to suffer TBI from all causes each year, with the Southeast Asian and Western Pacific regions experiencing the greatest overall burden of disease. Head injury following road traffic collision is more common in LMICs, and the proportion of TBIs secondary to road traffic collision is likewise greatest in these countries. Meanwhile, the estimated incidence of TBI is highest in regions with higher-quality data, specifically in North America and Europe.