Stress injuries typically develop as a result of overuse and lack of recovery. However, despite a 7-year stress fracture incidence rate of approximately 40%, in vivo bone stresses and strains do not approach levels of ultimate strength. Therefore, there must be outside factors such as muscle fatigue which lead to increased strain and injury risks. PURPOSE: Muscle fatigue during a long distance run may lead to increased bone strain in the tibia, and result in increased injury risk. METHODS: Sixteen runners did a graded treadmill test to determine max heart rate and VO2,max, which were then used to set the fatiguing speed for the long distance run. Before and after the fatiguing run, participants completed 10 trials over the force platform and through the field of view of an eight camera system within 5% of the fatiguing speed and with the right foot hitting the platform. Stance phase was analyzed for joint, muscle and contact forces. These forces were then distributed on an individually scaled finite element model (FEM) tibia and the peak principal strain location and magnitude were determined. The magnitude and location of pre- and post-principal strain and von Mises equivalent strain were compared using a repeated measures t-test. RESULTS: Peak principal strains in both compression and tension were significantly reduced at the point of peak contact forces (P < 0.001). In addition, von Mises equivalent strains decreased significantly at the 95th percentile and median values (P< 0.001). CONCLUSION: The hypothesis that strain magnitude would increase as a result of fatigue was not supported. Several variables such as triceps surae muscle force, vertical stiffness, and step width were altered by the run but none of these changes reached statistical significance. Model inputs were slightly decreased, and perhaps may have been the reason for the decrease. Further research is necessary to determine the exact reason. Limitations for this study included not including a fibula in the model, maintaining bone properties from pre- to post-fatigue, and a lack of quantification of fatigue.