ABSTRACTIntroduction: Neuromuscular electrical stimulation (NMES) can be delivered over a muscle belly (mNMES) or nerve trunk (nNMES). Both methods generate contractions that fatigue rapidly due, in part, to non‐physiologically high motor unit (MU) discharge frequencies. In this study we introduce interleaved NMES (iNMES), whereby stimulus pulses are alternated between mNMES and nNMES. iNMES was developed to recruit different MU populations with every other stimulus pulse, with a goal of reducing discharge frequencies and muscle fatigue. Methods: Torque and electromyography were recorded during fatigue protocols (12 min, 240 contractions) delivered using mNMES, nNMES, and iNMES. Results: Torque declined significantly 3 min into iNMES and 1 min into both mNMES and nNMES. Torque decreased by 39% during iNMES and by 67% and 58% during mNMES and nNMES, respectively. Conclusions: iNMES resulted in less muscle fatigue than mNMES and nNMES. Delivering NMES in ways that reduce MU discharge frequencies holds promise for reducing muscle fatigue during NMES‐based rehabilitation. Muscle Nerve, 2016 Muscle Nerve 55: 179–189, 2017