Objectives This study investigated whether six weeks of resistance training to concentric failure performed with either a moderate (10-repetition maximum) or high (20-repetition maximum) repetition range enhances skeletal muscle oxidative capacity, hypertrophy, and strength. Design A pre–post intervention study with a randomized group allocation. Methods Forty-seven healthy young men were randomly allocated to a 10-repetition maximum group (n = 16), 20-repetition maximum group (n = 16), or non-training control group (n = 15) and completed 12 supervised lower-body sessions. Vastus lateralis oxidative capacity was assessed using near-infrared spectroscopy during transient arterial occlusion. Recovery kinetics of muscle O2 consumption were modeled mono-exponentially, and the time constant served as an index of oxidative capacity. The secondary outcomes were ultrasound-derived muscle thickness and multi-joint 10-repetition maximum strength. Results Both training groups showed significantly reduced time constant compared to the control group (10-repetition maximum: −18.9 %; 20-repetition maximum: −29.1 %; p textless 0.05), with no difference between repetition ranges (p = 0.356). Vastus lateralis thickness increased similarly in the 10-repetition maximum and 20-repetition maximum groups (p textless 0.001 vs. control), while strength improved across all exercises in the two experimental groups; only the lying leg-curl favored 20-repetition maximum over 10-repetition maximum (p = 0.015). Conclusions These findings demonstrate that twice-weekly resistance training to failure, irrespective of whether ~10 or ~20 repetitions are used, simultaneously enhances mitochondrial oxidative capacity, muscle hypertrophy, and strength, underscoring the versatility of resistance training for performance optimization and interventions targeting improved metabolic health.