Objective: Traumatic brain injury (TBI) is a major cause of death and disability, leading to great personal suffering and huge costs to society. Integrated knowledge on epidemiology, economic consequences and disease burden of TBI is scarce but essential for optimizing healthcare policy and preventing TBI. This study aimed to estimate incidence, cost-of-illness and disability-adjusted life years (DALYs) of TBI in the Netherlands. Methods: This study included data on all TBI patients who were treated at an Emergency Department (ED - National Injury Surveillance System), hospitalized (National Medical Registration), or died due to their injuries in the Netherlands between 2010-2012. Direct healthcare costs and indirect costs were determined using the incidence-based Dutch Burden of Injury Model. Disease burden was assessed by calculating years of life lost (YLL) owing to premature death, years lived with disability (YLD) and DALYs. Incidence, costs and disease burden were stratified by age and gender. Results: TBI incidence was 213.6 per 100,000 person years. Total costs were (sic)314.6 (USD $433.8) million per year and disease burden resulted in 171,200 DALYs (on average 7.1 DALYs per case). Men had highest mean costs per case ((sic)19,540 versus (sic)14,940), driven by indirect costs. 0-24-year-olds had high incidence and disease burden but low economic costs, whereas 25-64-year-olds had relatively low incidence but high economic costs. Patients aged 65+ had highest incidence, leading to considerable direct healthcare costs. 0-24-year-olds, men aged 25-64 years, traffic injury victims (especially bicyclists) and home and leisure injury victims (especially 0-5-year-old and elderly fallers) are identified as risk groups in TBI. Conclusions: The economic and health consequences of TBI are substantial. The integrated approach of assessing incidence, costs and disease burden enables detection of important risk groups in TBI, development of prevention programs that target these risk groups and assessment of the benefits of these programs.