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Background Well-advised priority setting in prevention and treatment of injuries relies on detailed insight into costs of injury. This study aimed to provide a detailed overview of medical and productivity costs due to injury up to two years post-injury and compare these costs across subgroups for injury severity and age. Methods A prospective longitudinal cohort study followed all adult (≥18 years) injury patients admitted to a hospital in Noord-Brabant, the Netherlands. Patients filled out questionnaires 1 week, 1, 3, 6, 12 and 24 months after trauma, including items on health care consumption from the medical consumption questionnaire (iMCQ) and productivity loss from the productivity cost questionnaire (PCQ). Furthermore, injury severity was defined by Injury Severity Score (ISS). Data on diagnostics was retrieved from hospital registries. We calculated medical costs, consisting of in-hospital costs and post-hospital medical costs, and productivity costs due to injury up to two years post-injury. Results Approximately 50% (N = 4883) of registered patients provided informed consent, and 3785 filled out at least one questionnaire. In total, the average costs per patient were €12,190. In-hospital costs, post-hospital medical costs and productivity costs contributed €4810, €5110 and €5830, respectively. Total costs per patient increased with injury severity, from €7030 in ISS1-3 to €23,750 in ISS16+ and were lowest for age category 18-24y (€7980), highest for age category 85 years and over (€15,580), and fluctuated over age groups in between. Conclusion Both medical costs and productivity costs generally increased with injury severity. Furthermore, productivity costs were found to be a large component of total costs of injury in ISS1-8 and are therefore a potentially interesting area with regard to reducing costs.