Kwak, M, Succi, PJ, Benitez, B, Mitchinson, C, Samaan, MA, Abel, MG, and Bergstrom, HC. Comparison of force, neuromuscular, and metabolic responses during sustained, isometric handgrip holds to failure anchored to low and high perceptual intensities in men: An exploratory study. J Strength Cond Res 38(8): e405–e416, 2024—This study examined the responses of force alterations, relative to critical force (CF), neuromuscular parameters, and muscle oxygenation (SmO2) for isometric handgrip holds to failure (HTF) anchored to ratings of perceived exertion (RPE) of 3 and 7. Twelve men completed pre-maximal voluntary isometric contractions (pre-MVIC), submaximal HTF at 4 percentages of pre-MVIC, HTF at RPE = 3 and 7, and post-MVIC. Mechanomyograpic (MMG) signals and SmO2 were recorded during the RPE HTF. Analyses included paired-samples t-tests and repeated-measures ANOVAs at an alpha level of p ≤ 0.05. Time to task failure was not different between RPE 3 (478.7 ± 196.6 s) and RPE 7 (495.8 ± 173.8 s). Performance fatigability (PF) and MMG amplitude (AMP) were greater for RPE 7 (PF: 37.9 ± 12.9%; MMG AMP: 15.7 ± 7.4% MVIC) than RPE 3 (PF: 30.0 ± 14.5%; MMG AMP: 10.2 ± 6.5% MVIC), but MMG mean power frequency (MPF) was greater for RPE 3 (146.2 ± 31.1% MVIC) than RPE 7 (128.8 ± 23.0% MVIC). There were RPE-dependent decreases in force (p ≤ 0.01) across 3 discernable phases during the HTF. There were decreases in MMG AMP across time for both RPEs, but there were no significant changes in MMG MPF or SmO2. There were overall similar motor unit control strategies and local metabolic demand between RPEs. The majority of the HTF performed below CF at RPE 3 and 7 indicated CF did not reflect the highest sustainable force. When prescribing isometric exercise anchored to RPE, practitioners should be aware of the magnitude of force loss and relative intensity of the task to be sure desired training loads are met.