Objective: To identify physical and behavioral characteristics related to the incidence of tibial stress injuries (TSIs). Design: Case-control study. No clinical care was conducted. Setting: Research laboratories in the San Francisco (the United States) and Gold Coast (Australia) areas. Participants: Forty-eight patients (21 men and 27 women) with acute TSI, and 36 (16 men and 20 women) age-matched, sex-matched, height-matched, weight-matched, and activity-matched controls with no history of TSI. Independent Variables: Height, weight, body mass index, bone, lean and fat mass, lower limb alignment anomalies, foot type, orthotics, calcium, recent weight change, menstrual history, oral contraceptive use, medications, smoking, alcohol, sleep, training type, and intensity. Differences in continuous variables were tested using 1-way analysis of variance. Categorical variable comparisons were performed with Fisher exact test. Main Outcome Measure: Tibial stress injury. Results: Tibial stress injury cases had 2.7% more fat (P < 0.001) and 2.6% less muscle (P < 0.001) as well as lower trochanteric bone mineral content (BMC) (P < 0.001), lumbar spine (LS) area (P < 0.001), femoral neck BMC (P < 0.001), length (P < 0.05), area (P < 0.001), cortical width (P < 0.01), cross-sectional moment of inertia (P < 0.001), and index of bending strength (P < 0.001) than controls. Controls had lower LS BMC (P < 0.01), length (P < 0.001), and broadband ultrasound attenuation (P < 0.001). The use of orthotic insoles was more prevalent in TSI cases than controls (25% vs 5.6%, respectively; P < 0.02), as were foot anomalies (56.3% vs 27.8%, respectively; P = 0.01). Conclusions: Tibial stress injury cases had lower lean and higher fat mass, a tendency for smaller bones, and for foot anomalies compared with uninjured matched controls. bone mineral density was normal for both groups. Clinical Relevance: Enhancing lean mass and limiting gains in fat may provide some protection against TSI. Individuals with small skeletal frames are advised to increase training loads particularly gradually and to reduce training intensity at the first sign of pain in the shins.