Background Running-related injuries (RRIs) are a prevalent issue for runners, with several factors proposed to be causative. The majority of studies to date are limited by retrospective study design, small sample sizes and seem to focus on individual risk factors in isolation. This study aims to investigate the multifactorial contribution of risk factors to prospective RRIs. Methods Recreational runners ( n = 258) participated in the study, where injury history and training practices, impact acceleration, and running kinematics were assessed at a baseline testing session. Prospective injuries were tracked for one year. Univariate and multivariate Cox regression was performed in the analysis. Results A total of 51% of runners sustained a prospective injury, with the calf most commonly affected. Univariate analysis found previous history of injury < 1 year ago, training for a marathon, frequent changing of shoes (every 0–3 months), and running technique (non-rearfoot strike pattern, less knee valgus, greater knee rotation) to be significantly associated with injury. The multivariate analysis revealed previous injury, training for a marathon, less knee valgus, and greater thorax drop to the contralateral side to be risk factors for injury. Conclusion This study found several factors to be potentially causative of injury. With the omission of previous injury history, the risk factors (footwear, marathon training and running kinematics) identified in this study may be easily modifiable, and therefore could inform injury prevention strategies. This is the first study to find foot strike pattern and trunk kinematics to relate to prospective injury.