Background: Running-related injuries (RRIs) occur when load exceeds tissue strength and therefore, purportedly result from a complex interaction of factors. However, research regarding factors associated with RRI remains inconclusive. Very few prospective, multifactorial, large-scale studies exist exploring general or specific RRIs, with even fewer examining segmental loading and running technique throughout the body. Additionally, although runners who have never been injured or have not been recently injured may have distinctive factors explaining their resistance to (re-)injury, this has seldom been examined. Aims: Primary aim: To prospectively investigate factors associated with general and specific RRIs using a multifactorial, large-scale approach. Secondary aim: To retrospectively investigate differences in clinical and loading factors between injury-resistant and recently injured runners. Methods: This thesis incorporates work from four research questions (Chapters 3, 4, 5, 6) and one methodological chapter (Section 8.3). A baseline assessment of 274 recreational runners examined: (1) loading (via impact accelerations), (2) running technique (via motion analysis) and (3) clinical measures of: strength, range of motion and foot alignment, (4) demographics and injury and training history. RRIs were tracked for one year. Results: There was a 1-year incidence of general RRI of 52%, and 14% for calf-complex injury. Prospectively, running technique and foot alignment were associated with both general (Chapter 5) and calf-complex injuries (Chapter 6). Some factors were injury-specific, including running pace and sagittal plane motion. Overall, there was a limited potential identified for the use of any measure in RRI screening. Retrospectively, recently injured runners displayed greater lower back loading compared to those injured >2 years ago and strength differences (plantar flexion and hip abduction) were noted among runners with and without a history of RRI (Chapters 3,4). Conclusion: This thesis adds important insights into potential factors that are associated with RRIs. These may form the basis of intervention programmes.