Athletes, especially female athletes, experience high rates of tibial bone stress injuries (BSIs). Knowledge of tibial loads during walking and running is needed to understand injury mechanisms and design safe running progression programs. To examine tibial loads as a function of gait speed in male and female runners. Controlled laboratory study. Kinematic and kinetic data were collected on 40 recreational runners (20 female, 20 male) during 4 instrumented gait speed conditions on a treadmill (walk, preferred run, slow run, fast run). Musculoskeletal modeling, using participant-specific magnetic resonance imaging and motion data, was used to estimate tibial stress. Peak tibial stress and stress-time impulse were analyzed using 2-factor multivariate analyses of variance (speed*sex) and post hoc comparisons (α = .05). Bone geometry and tibial forces and moments were examined. Peak compression was influenced by speed (P < .001); increasing speed generally increased tibial compression in both sexes. Women displayed greater increases in peak tension (P = .001) and shear (P < .001) than men when transitioning from walking to running. Further, women displayed greater peak tibial stress overall (P < .001). Compressive and tensile stress-time impulse varied by speed (P < .001) and sex (P = .006); impulse was lower during running than walking and greater in women. A shear stress-time impulse interaction (P < .001) indicated that women displayed greater impulse relative to men when changing from a walk to a run. Compared with men, women displayed smaller tibiae (P < .001) and disproportionately lower tibial forces (P≤ .001-.035). Peak tibial stress increased with gait speed, with a 2-fold increase in running relative to walking. Women displayed greater tibial stress than men and greater increases in stress when shifting from walking to running. Sex differences appear to be the result of smaller bone geometry in women and tibial forces that were not proportionately lower, given the womens' smaller stature and lower mass relative to men. These results may inform interventions to regulate running-related training loads and highlight a need to increase bone strength in women. Lower relative bone strength in women may contribute to a sex bias in tibial BSIs, and female runners may benefit from a slower progression when initiating a running program.