Background Progressive overload is a principle of resistance training exercise program design that typically relies on increasing load to increase neuromuscular demand to facilitate further adaptations. However, little attention has been given to another way of increasing demand—increasing the number of repetitions. Objective This study aimed to compare the effects of two resistance training programs: (1) increasing load while keeping repetition range constant vs (2) increasing repetitions while keeping load constant. We aimed to compare the effects of these programs on lower body muscle hypertrophy, muscle strength, and muscle endurance in resistance-trained individuals over an 8-week study period. Methods Forty-three participants with at least 1 year of consistent lower body resistance training experience were randomly assigned to one of two experimental, parallel groups: A group that aimed to increase load while keeping repetitions constant (LOAD: n = 22; 13 men, nine women) or a group that aimed to increase repetitions while keeping load constant (REPS: n = 21; 14 men, seven women). Subjects performed four sets of four lower body exercises (back squat, leg extension, straight-leg calf raise, and seated calf raise) twice per week. We assessed one repetition maximum (1RM) in the Smith machine squat, muscular endurance in the leg extension, countermovement jump height, and muscle thickness along the quadriceps and calf muscles. Between-group effects were estimated using analyses of covariance, adjusted for pre-intervention scores and sex. Results Rectus femoris growth modestly favored REPS (adjusted effect estimate (CI90%), sum of sites: 2.8 mm [−0.5, 5.8]). Alternatively, dynamic strength increases slightly favored LOAD (2.0 kg [−2.4, 7.8]), with differences of questionable practical significance. No other notable between-group differences were found across outcomes (muscle thicknesses, <1 mm; endurance, <1%; countermovement jump, 0.1 cm; body fat, <1%; leg segmental lean mass, 0.1 kg), with narrow CIs for most outcomes. Conclusion Both progressions of repetitions and load appear to be viable strategies for enhancing muscular adaptations over an 8-week training cycle, which provides trainers and trainees with another promising approach to programming resistance training.