BACKGROUND: Traumatic brain injury (TBI) is the main cause of mortality and severe morbidity in cyclists admitted to Dutch emergency departments (EDs). Although the use of bicycle helmets is an effective way of preventing TBI, this is uncommon in the Netherlands. An option to increase its use is through a legal enforcement. However, little is known about the cost-effectiveness of such mandatory use of helmets in the Dutch context. The current study aimed to assess the cost-effectiveness of a law that enforces helmet use to reduce TBI and TBI-related mortality. METHODS: The cost-effectiveness was estimated through decision tree modelling. In this study, wearing bicycle helmets enforced by law was compared with the current situation of infrequent voluntary helmet use. The total Dutch cycling population, consisting of 13.5 million people, was included in the model. Model data and parameters were obtained from Statistics Netherlands, the National Road Traffic Database, Dutch Injury Surveillance System, and literature. Effects included were numbers of TBI, death, and disability-adjusted life years (DALY). Costs included were healthcare costs, costs of productivity losses, and helmet costs. Sensitivity analysis was performed to assess which parameter had the largest influence on the incremental cost-effectiveness ratio (ICER). RESULTS: The intervention would lead to an estimated reduction of 2942 cases of TBI and 46 deaths. Overall, the incremental costs per 1) death averted, 2) per TBI averted, and 3) per DALY averted were estimated at 1) € 2,002,766, 2) € 31,028 and 3) € 28,465, respectively. Most favorable were the incremental costs per DALY in the 65+ age group: € 17,775. CONCLUSIONS: The overall costs per DALY averted surpassed the Dutch willingness to pay threshold value of € 20,000 for cost-effectiveness of preventive interventions. However, the cost per DALY averted for the elderly was below this threshold, indicating that in this age group largest effects can be reached. If the price of a helmet would reduce ...