METHODS Controlled laboratory study. OBJECTIVE To compare the changes in lower limb sagittal kinematics in running after a knee fatigue protocol with those observed after an ankle fatigue protocol. BACKGROUND Impaired force-generating ability of specific muscles may affect running mechanics, with negative implications for injury occurrence and performance. Identifying the strategies used to compensate for fatigue of selected muscles may assist in the design of more effective exercise programs for injury prevention and performance enhancement in running. METHODS Sagittal plane kinematic data and the electromyographic (EMG) signal of the vastus medialis (VM), gastrocnemius (GAS), and biceps femoris (BF) muscles were collected from 15 females running at 3.61 m/s on a treadmill prior to, and following, an isokinetic knee extension/flexion and, on a separate day, an ankle plantar flexion/dorsiflexion fatigue protocol performed at 120 degrees/s. RESULTS Ankle muscle fatigue caused decreased ankle dorsiflexion, while knee fatigue caused increased knee flexion at initial contact (P<.05). Both protocols increased knee flexion angle at toe-off, as well as the amplitude of GAS and VM EMG signal, with the hip more extended after knee fatigue and the ankle more plantar flexed after ankle muscle fatigue. Ankle muscle fatigue caused a significant increase in hip extensionand ankle plantar flexion angular velocity, and a decline of BF EMG signal during the swing phase (P<.05). Knee muscle fatigue decreased hip and knee flexion angular velocity and increased BF EMG signal during the swing phase (P<.05). CONCLUSIONS Localized muscle fatigue effects on sagittal kinematics differed between the 2 protocols. However, the strategy used to compensate for fatigue was similar for both protocols: to protect the joints at initial impact and to prevent impairments in performance during toeoff and swing phase.