The purpose was to examine the effects of equal volume, high-repetition resistance training (HRRT) to volitional fatigue, with different workout frequency, on muscle mass and muscle performance in healthy postmenopausal women. After matching participants for age, weight and years post-menopause, postmenopausal women were randomized to perform HRRT two days per week (HRRT-2; 60.8 ± 5.5 years, 72.1 ± 16.4 kg, 160.2 ± 3.9 cm; 3 sets of 20-30 repetitions/set to volitional fatigue for elbow and knee flexion and extension) or three days per week (HRRT-3; 61.8 ± 4.6 years, 67.6 ± 13.6 kg, 160.7 ± 4.4 cm; 2 sets of 20-30 repetitions/set to volitional fatigue per exercise) for 8 weeks. Prior and following training, assessments were made for muscle thickness of the elbow and knee flexors and extensors (B-mode ultrasound), muscle strength (1-repetition maximum for elbow and knee flexion and extension), and muscle endurance (maximum number of repetitions performed at 50% baseline 1-repetition maximum for elbow and knee flexion and extension). There was a significant increase over time for all measures of muscle thickness, muscle strength, and muscle endurance (p < 0.001), with no differences between groups. Equal volume, HRRT (independent of training frequency), is an effective intervention for improving muscle mass and muscle performance in postmenopausal women.