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This study aimed to investigate how facilitatory and inhibitory KT of the Vastus Medialis affected the activation and the fatigue indices of VM, Vastus Lateralis (VL) and Rectus Femoris (RF) throughout a dynamic fatigue protocol. Seventeen collegiate athletes (Ten males, seven females, age: 24.76 ± 3.99 years, height: 1.73 ± 0.10 m, mass: 68.11 ± 8.54 kg) voluntarily participated in four dynamic fatigue protocol sessions in which no-tape (control condition), inhibitory, facilitatory and sham KTs were applied to the Vastus Medialis in each session. The protocol included 100 dynamic maximum concentric knee extensions at 90°/s using an isokinetic dynamometry device. The knee extensor muscle activities were recorded using wireless surface electromyography. The average muscle activity (Root mean square) during the first three repetitions and the repetitions number of 51–100, respectively, were used to calculate the before and after exhaustion muscle activity. Furthermore, median frequency slope during all repetitions was reported as the fatigue rate of muscles during different KT conditions and for the control condition (no-tape). The results showed neither muscle activation (significance for the main effect of KT; VM = 0.82, VL = 0.72, RF = 0.19) nor fatigue rate (significance for the main effect of KT; VM = 0.11 VL = 0.71, RF = 0.53) of the superficial knee extensor muscles were affected in all four conditions. These findings suggest that the direction of KT cannot reduce, enhance muscle activity or cause changes in muscle exhaustion. Future studies should investigate the generalizability of current findings to other populations.