Background: Trailrunning is becoming very popular. However, the risk and burden of running-related injuries (RRI) in trailrunning is not well established. Objective: To investigate the prevalence, injury rate, severity, nature, and economic burden of RRIs in Dutch trailrunners. Methods: This prospective cohort study included 228 trailrunners aged 18 years or over (range 23–67), and was conducted between October 2013 and December 2014. After completing the baseline questionnaire, the Oslo Sports Trauma Research Center Questionnaire on Health Problems was administered every 2 weeks to collect data on RRIs. Participants who reported RRIs were asked about healthcare utilization (direct costs) and absenteeism from paid work (indirect costs). RRI was defined as disorders of the musculoskeletal system or concussions experienced or sustained during participation in running. Results: The mean prevalence of RRIs measured over time was 22.4 % [95 % confidence interval (CI) 20.9–24.0], and the injury rate was 10.7 RRIs per 1000 h of running (95 % CI 9.4–12.1). The prevalence was higher for overuse (17.7 %; 95 % CI 15.9–19.5) than for acute (4.1 %; 95 % CI 3.3–5.0) RRIs. Also, the injury rate was higher for overuse (8.1; 95 % CI 6.9–9.3) than for acute (2.7; 95 % CI 2.0–3.4) RRIs. The median of the severity score was 35.0 [25–75 %, interquartile range (IQR) 22.0–55.7], and the median of the duration of RRIs was 2.0 weeks (IQR 2.0–6.0) during the study. The total economic burden of RRIs was estimated at €172.22 (95 % CI 117.10–271.74) per RRI, and €1849.49 (95 % CI 1180.62–3058.91) per 1000 h of running. An RRI was estimated to have a direct cost of €60.92 (95 % CI 45.11–94.90) and an indirect cost of €111.30 (95 % CI 61.02–192.75). Conclusions: The health and economic burden of RRIs presented in this study are significant for trailrunners and for society. Therefore, efforts should be made in order to prevent RRIs in trailrunners. © 2016, The Author(s).