The goal of this research was to analyze the effects of fatigue on the shock waves generated by foot strike. Twenty-two subjects were instrumented with an externally attached, lightweight accelerometer placed over the tibial tuberosity. The subjects ran on a treadmill for 30 min at a speed near their anaerobic threshold. Fatigue was established when the end-tidal CO2 pressure decreased. The results indicated that approximately half of the subjects reached the fatigue state toward the end of the test. Whenever fatigue occurred, the peak acceleration was found to increase. It was thus concluded that there is a clear association between fatigue and increased heel strike–induced shock waves. These results have a significant implication for the etiology of running injuries, since shock wave attenuation has been previously reported to play an important role in preventing such injuries.