Although from an athletic performance perspective it may be beneficial to undertake drop jump training when fatigued (principle of "specificity" of training), such endurance fatigue may expose the body to a greater risk of injury if it causes an increase in peak impact accelerations. This study aimed to determine if endurance fatigue resulted in an increase in tibial peak impact acceleration and an associated change in knee kinematics when completing plyometric drop jumps. Fifteen females performed drop jumps from 3 heights (15, 30, and 45 cm) when fatigued and nonfatigued. Treadmill running was used to induce endurance fatigue. The following variables were assessed: tibial peak impact acceleration, knee angle at initial ground contact, maximum angle of flexion, range of flexion, and peak knee angular velocity. Fatigue resulted in significantly greater (p < 0.05) tibial peak impact acceleration and knee flexion peak angular velocity in drop jumps from 15 and 30 cm, but not from 45 cm. Fatigue had no effect on any of the knee angles assessed. The neuromuscular system was affected negatively by endurance fatigue at 15 and 30 cm, indicating that coaches should be aware of a potential increased risk of injury in performing drop jumps when fatigued. Because from the greater drop height of 45 cm the neuromuscular system had a reduced capacity to attenuate the impact accelerations per se, whether nonfatigued or fatigued, this would suggest that this height may have been too great for the athletes examined.