Tibial stress fracture is a common injury in runners and military personnel. Elevated bone strain is believed to be associated with the development of stress fractures and is influenced by bone geometry and density. The purpose of this study was to characterize tibial-fibular geometry and density variations in young active adults, and to quantify the influence of these variations on finite element-predicted bone strain. A statistical appearance model characterising tibial-fibular geometry and density was developed from computed tomography scans of 48 young physically active adults. The model was perturbed ±1 and 2 standard deviations along each of the first five principal components to create finite element models. Average male and female finite element models, controlled for scale, were also generated. Muscle and joint forces in running, calculated using inverse dynamics-based static optimization, were applied to the finite element models. The resulting 95th percentile pressure-modified von Mises strain (peak strain) and strained volume (volume of elements above 4000 με) were quantified. Geometry and density variations described by principal components resulted in up to 12.0% differences in peak strain and 95.4% differences in strained volume when compared to the average tibia-fibula model. The average female illustrated 5.5% and 41.3% larger peak strain and strained volume, respectively, when compared to the average male, suggesting that sexual dimorphism in bone geometry may indeed contribute to greater stress fracture risk in females. Our findings identified important features in subject-specific geometry and density associated with elevated bone strain that may have implications for stress fracture risk.