This study compared the effects of four different resistance training (RT) programs that differed in the movement velocity [maximum (MaxV) vs. 50% of maximum voluntary velocity (HalfV)] and the blood flow condition [free (FF) vs. restricted (BFR)] on strength, neuromuscular, and hypertrophy adaptations. Fortysix resistance-trained males were randomly assigned to one of the four abovementioned protocols. Subjects followed an 8-week RT program, twice per week, with similar intensity (55%–65% 1RM), sets (3), and repetitions per set (10–6) in the full-squat (SQ) exercise. Before and after the RT program, they were evaluated for: 1) muscle size of the vastus lateralis; 2) vertical jump; 3) maximal isometric contraction; 4) progressive loading test; and 5) fatigue test, in SQ. Electromyographic (EMG) activity was assessed during all SQ tests. All protocols exhibited significant gains in strength-derived parameters without significant differences between groups. A BFR × VEL × time interaction (p = 0.05) was observed for countermovement jump, with improvements in the HalfV-BFR and MaxV-FF protocols. A VEL × time interaction (p = 0.03) was found for the EMG amplitude under light loads, since HalfV-BFR increased its values. MaxV-BFR and HalfV-FF induced greater hypertrophy in the distal region of the vastus lateralis (BFR × VEL × time interaction, p = 0.04), with MaxV-BFR producing the greatest gains in all sections. Both MaxV-FF and HalfV-BFR increased CMJ height. HalfV-BFR also increased neuromuscular activity against light loads. MaxV-BFR and HalfV-FF evoked higher hypertrophy in muscle size, with the greatest gains in muscle size with MaxV-BFR.