Background: Behavioral and social science theories/models have been gaining attention in sports injury prevention. Objective: To investigate the potential of the Theory of Planned Behavior in explaining running-related injury preventive behavior. Methods: Six-month prospective cohort study based on data gathered from a randomized controlled trial. From a total of 1512 invited trail runners, 232 were included in this study. Preventive behaviors and their determinants were assessed at baseline and two and six months after baseline. Five-point Likert scales were used to assess the determinants of preventive behavior. A Bayesian path analysis was conducted applying mixed models and mediation analysis. Results: A 1-point increase in intention, attitude, subjective norm, and perceived behavioral control predicted an increase of 54% (95% Bayesian credible interval [BCI]: 38, 71) in the rate of performing running-related injury preventive behavior, explaining 49% (R2 0.49; 95% BCI: 0.41, 0.56) of the variance around preventive behavior. Intention and perceived behavioral control predicted running-related injury preventive behavior directly, while 40% (95% BCI: 21, 61) and 44% (95% BCI: 20, 69) of the total effect of attitude was mediated by intention and perceived behavioral control, respectively. Attitude, subjective norm, and perceived behavioral control predicted intention. Conclusions: The Theory of Planned Behavior may have the potential to explain half of the variance around running-related injury preventive behavior and intention. Therefore, such theory may be considered a relevant and useful tool in developing, investigating, and/or implementing programs aimed at preventing running-related injuries.