BACKGROUND: Trail running is popular worldwide, but there is no preventive intervention for running-related injury (RRI). AIM: To evaluate the effectiveness of adding online tailored advice (TrailS6 ) to general advice on (1) the prevention of RRIs and (2) the determinants and actual preventive behaviour in Dutch trail runners. METHODS: Two-arm randomised controlled trial over 6 months. 232 trail runners were randomly assigned to an intervention or control group. All participants received online general advice on RRI prevention 1 week after baseline. Every 2 weeks, participants in the intervention group received specific advice tailored to their RRI status. The control group received no further intervention. Bayesian mixed models were used to analyse the data. RESULTS: Trail runners in the intervention group sustained 13% fewer RRIs compared with those in the control group after 6 months of follow-up (absolute risk difference -13.1%, 95% Bayesian highest posterior credible interval (95% BCI) -23.3 to -3.1). A preventive benefit was observed in one out of eight trail runners who had received the online tailored advice for 6 months (number needed to treat 8, 95% BCI 3 to 22). No significant between-group difference was observed on the determinants and actual preventive behaviours. CONCLUSIONS: Online tailored advice prevented RRIs among Dutch trail runners. Therefore, online tailored advice may be used as a preventive component in multicomponent RRI prevention programmes. No effect was observed on determinants and actual preventive behaviours. TRIAL REGISTRATION NUMBER: The Netherlands National Trial Register (NTR5431).