This study aimed to compare the effects of 2 resistance training (RT) programs with different velocity losses (VLs) allowed in each set: 10% (VL10%) versus 30% (VL30%) on neuromuscular performance and hormonal response. Twenty-five young healthy males were randomly assigned into 2 groups: VL10% (n = 12) or VL30% (n = 13). Subjects followed a velocity-based RT program for 8 weeks (2 sessions per week) using only the full-squat (SQ) exercise at 70%–85% 1-repetition maximum (1RM). Repetition velocity was recorded in all training sessions. A 20-m running sprint, countermovement jump (CMJ), 1RM, muscle endurance, and electromyogram (EMG) during SQ exercise and resting hormonal concentrations were assessed before and after the RT program. Both groups showed similar improvements in muscle strength and endurance variables (VL10%: 7.0%–74.8%; VL30%: 4.2%–73.2%). The VL10% resulted in greater percentage increments in CMJ (9.2% vs. 5.4%) and sprint performance (–1.5% vs. 0.4%) than VL30%, despite VL10% performing less than half of the repetitions than VL30% during RT. In addition, only VL10% showed slight increments in EMG variables, whereas no significant changes in resting hormonal concentrations were observed. Therefore, our results suggest that velocity losses in the set as low as 10% are enough to achieve significant improvements in neuromuscular performance, which means greater efficiency during RT. Novelty The VL10% group showed similar or even greater percentage of changes in physical performance compared with VL30%. No significant changes in resting hormonal concentrations were observed for any training group. Curvilinear relationships between percentage VL in the set and changes in strength and CMJ performance were observed.