The following graduate thesis aims to identify important clinical variables, including injury, treatment and healing characteristics, that serve as prognostic indicators for complications in patients with fractures of the tibial shaft. In particular, the complications of focus in this thesis are surgical site infections and nonunion. The three analytical studies comprising this thesis were derived from large data sets arising from two randomized controlled trials and an observational cohort study. The first chapter (Open Tibial Fractures: Updated Guidelines for Management) is a published literature review that provides an overall introduction to the thesis. It highlights the paucity of high-quality evidence currently available to inform many of the treatment strategies for patients with open fractures of the tibial shaft. The second chapter (Timing of Irrigation & Debridement and Infection Risk in Severe Open Fractures) is a sub-study of all open fracture patients recruited in the International Orthopaedic Multicenter Study (INORMUS) in Fracture Care. The findings of this study suggest that timing delays to irrigation and debridement for patients with open fracture injuries is associated with an increased risk of surgical site infection. The third and fourth chapters evaluate the association between early healing measures and nonunion in patients with tibial fractures. Specifically, chapter three (Exploring the Association of 3-Month Radiographic Union Score for Tibia Fractures (RUST) with Nonunion in Tibial Shaft Fracture Patients) demonstrates that radiographic healing at three months post-operatively is strongly associated with nonunion at one year. Similarly, chapter four (Nonunion in Patients with Tibial Shaft Fractures—Can Early Functional Status Predict Healing?) demonstrates that functional status at three months post-operatively is also correlated to eventual healing. Both of these studies include patients from the randomized controlled trials, SPRINT (Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures) and FLOW (Fluid Lavage of Open Wounds). / Thesis / Master of Science (MSc) / The enclosed thesis work evaluates outcomes in patients with fractures primarily of the tibial shaft. In particular, the comprised studies assess whether certain characteristics, such as injury factors, treatment variables and early healing progression, are associated with adverse outcomes in these patients. One study found that delays in timing to appropriate surgical care for patients with open fractures (open wound at the site of the fracture) leads to greater risk of infection. Furthermore, two studies found that both the level of radiographic healing and functional status of patients at three months from surgery can help predict if the patient will ultimately heal radiographically at one year from injury. The findings of this thesis work should help orthopaedic care providers identify patients at high risk for infections and nonunions, such that these patients can be closely monitored to minimize the risk of such complications.