Rodríguez-Rosell, D, Yáñez-García, JM, Mora-Custodio, R, Torres-Torrelo, J, Ribas-Serna, J, and González-Badillo, JJ. Role of the effort index in predicting neuromuscular fatigue during resistance exercises. J Strength Cond Res XX(X): 000-000, 2020-This study aimed: (a) to analyze the acute mechanical, metabolic, and electromyographic (EMG) response to 16 resistance exercise protocols (REPs) defined by the first repetition's mean velocity and the percentage of velocity loss (%VL) over the set in the full-squat (SQ) exercise; and (b) to assess whether the effort index (EI, the product of the first repetition's mean velocity and the %VL in the set) could be used as an objective indicator of neuromuscular fatigue. Eleven resistance-trained men performed 16 REPs in the SQ exercise. For the configuration of the 16 REPs, 4 relative intensities (50, 60, 70, and 80% 1 repetition maximum) and 4 magnitudes of %VL (∼10, ∼20, ∼30, and ∼45%) were used. The induced fatigue after each REP was quantified using the percentage of change in (a) countermovement jump (CMJ) height, (b) mean propulsive velocity attained with the load that elicited an ∼1.00 m·s (V1 m·s load), and (c) changes in surface EMG variables. Blood lactate concentration was also collected. The EI presented very strong relationships with the %VL with the V1 m·s load, CMJ height, and post-exercise lactate concentration (r = 0.92, 0.93, and 0.91, respectively; p < 0.001). Moderate to strong relationships were found between the EI and the changes in amplitude (r = 054-0.58; p < 0.05), frequency (r = -0.55 to -0.83; p < 0.05-0.001), and time-frequency (r = 0.52-0.77; p < 0.05-0.001) EMG variables. In addition, the moderate to strong relationships found between the relative changes in mechanical, metabolic, and EMG variables after each REP reinforce the validity of the EI as an objective indicator of muscle fatigue, metabolic stress, and neural effect induced by typical resistance training sessions. Thus, by adjusting the EI in each session, it is possible to quantifying the actual level of effort experienced by each individual during resistance exercises.