Cornejo-Daza, PJ, Sánchez-Valdepeñas, J, Páez-Maldonado, J, Rodiles-Guerrero, L, Boullosa, D, León-Prados, JA, Wernbom, M, and Pareja-Blanco, F. Acute responses to traditional and cluster-set squat training with and without blood flow restriction. J Strength Cond Res 38(8): 1401-1412, 2024-To compare the acute responses to different set configurations (cluster [CLU] vs. traditional [TRA]) under distinct blood flow conditions (free vs. restricted) in full-squat (SQ). Twenty resistance-trained males performed 4 protocols that differed in the set configuration (TRA: continuous repetitions; vs. CLU: 30 seconds of rest every 2 repetitions) and in the blood flow condition (FF: free-flow; vs. blood flow restriction [BFR]: 50% of arterial occlusion pressure). The relative intensity (60% 1RM), volume (3 sets of 8 repetitions), and resting time (2 minutes) were equated. Mean propulsive force (MPF), velocity (MPV) and power (MPP), and electromyography (EMG) parameters were recorded during each repetition. Tensiomyography (TMG), blood lactate, countermovement jump (CMJ) height, maximal voluntary isometric contraction, in SQ, and movement velocity against the load that elicited a 1 m·s -1 velocity at baseline (V1-load) in SQ were assessed at pre- and post-exercise. The CLU protocols allowed a better maintenance of MPF, MPV, MPP, and EMG median frequency during the exercise compared to TRA (clu-time interaction, p < 0.05). The TRA protocols experienced greater impairments post-exercise in TMG- and EMG-derived variables (clu-time interaction, p < 0.05) and SQ and CMJ performance (clu-time interaction, p = 0.08 and p < 0.05, respectively), as well as higher blood lactate concentrations (clu-time interaction, p < 0.001) than CLU. Moreover, BFR displayed decreases in TMG variables (bfr-time interaction, p < 0.01), but BFR-CLU resulted in the greatest reduction in twitch contraction time ( p < 0.001). Cluster sets reduced fatigue during and after the training session and BFR exacerbated impairments in muscle mechanical properties; however, the combination of both could improve contraction speed after exercise.