N euromuscular electrical stimulation (NMES) is a promising tool in the rehabilitation of individuals with a limited ability to activate their skeletal muscles, 13,35,36 as well as a method of strength training and short-term resistance training in athletic populations. 26,27 During NMES application, the capacity to maintain performance is compromised compared to voluntary exercise, Experimental laboratory study.The primary purpose was to investigate the independent effects of current amplitude, pulse duration, and current frequency on muscle fatigue during neuromuscular electrical stimulation (NMES). A second purpose was to determine if the ratio of the evoked torque to the activated area could explain muscle fatigue.Parameters of NMES have been shown to differently affect the evoked torque and the activated area. The efficacy of NMES is limited by the rapid onset of muscle fatigue.Seven healthy participants underwent 4 NMES protocols that were randomly applied to the knee extensor muscle group. The NMES protocols were as follows: standard protocol (Std), defined as 100-Hz, 450-μs pulses and amplitude set to evoke 75% of maximal voluntary isometric torque (MVIT); short pulse duration protocol (SP), defined as 100-Hz, 150-μs pulses and amplitude set to evoke 75% of MVIT; low-frequency protocol (LF), defined as 25-Hz, 450-μs pulses and amplitude set to evoke 75% of MVIT; and low-amplitude protocol (LA), defined as 100-Hz, 450-μs pulses and amplitude set to evoke 45% of MVIT. The peak torque was measured at the start and at the end of the 4 protocols, and percent fatigue was calculated. The outcomes of the 4 NMES protocols on the initial peak torque and activated cross-sectional area were recalculated from a companion study to measure torque per active area.Decreasing frequency from 100 to 25 Hz decreased fatigue from 76% to 39%. Decreasing the amplitude and pulse duration resulted in no change of muscle fatigue. Torque per active area accounted for 57% of the variability in percent fatigue between Std and LF protocols.Altering the amplitude of the current and pulse duration does not appear to influence the percent fatigue in NMES. Lowering the stimulation frequency results in less fatigue, by possibly reducing the evoked torque relative to the activated muscle area.