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).