BACKGROUND To identify persons at high risk of sustaining running-related injuries, an evidence-based understanding of the risk factors associated with injury is needed. OBJECTIVE To identify demographic and behavioral risk factors associated with running-related injuries. METHODS Observational prospective cohort study with a 1-year follow-up. METHODS Exposures including sex, age, body mass index (BMI), behavior (Type A Self-Rating Inventory [TASRI]), running experience, other sports activity, previous running-related injuries, and other injuries not related to running were assessed prior to or at baseline. The outcome of interest was a running-related injury, defined as any musculoskeletal complaint of the lower extremity or back caused by running that restricted the amount of running (volume, duration, pace, or frequency) for at least 1 week. All participants quantified their running volume by global positioning system (GPS) and used a neutral running shoe. Time to first injury for each exposure variable was analyzed using a generalized linear model, with cumulative kilometers of the training sessions as the time scale. RESULTS A total of 930 individuals were included in the study, of which 254 sustained a running-related injury during a total of 155.318 km of running. By calculating the cumulative injury risk differences (cIRDs) [95% confidence intervals] after 500 km of running, the TASRI Type B behavior (cIRD, 11.9% [-0.5%; 23.3%]; P = .04) was found to be a significant predictor of injury, while age between 45 and 65 years (cIRD, 14.7% [-2.1%; 31.5%]; P = .08) and previous injuries not related to running (cIRD, 11.1% [-0.2%; 22.4%]; P = .05) were considered clinically interesting, although not statistically significant. In addition, χ(2) test results across 4 BMI groups also revealed a borderline significant relationship (P = .06). No significant or clinically relevant relationships were found for sex (P = .42), previous running-related injury (P = .47), running experience (P = .30), and other sports activities (P = .30). CONCLUSIONS The findings of the present study suggest BMI >30 kg/m(2), age between 45 and 65 years, noncompetitive behavior, and previous injuries not related to running are associated with increased risk of injury among novice runners, while BMI <20 kg/m(2) was protective. Still, the role of the risk factors in the causal mechanism leading to injury needs to be investigated.