BACKGROUND: We have shown that combined caloric restriction (CR) and aerobic exercise training (AT) improve peak exercise O2 consumption (VO2peak), and quality-of-life in older patients with obese heart failure with preserved ejection fraction. However, ≈35% of weight lost during CR+AT was skeletal muscle mass. We examined whether addition of resistance training (RT) to CR+AT would reduce skeletal muscle loss and further improve outcomes. METHODS: This study is a randomized, controlled, single-blind, 20-week trial of RT+CR+AT versus CR+AT in 88 patients with chronic heart failure with preserved ejection fraction and body mass index (BMI) ≥28 kg/m2. Outcomes at 20 weeks included the primary outcome (VO2peak); MRI and dual X-ray absorptiometry; leg muscle strength and quality (leg strength ÷ leg skeletal muscle area); and Kansas City Cardiomyopathy Questionnaire. RESULTS: Seventy-seven participants completed the trial. RT+CR+AT and CR+AT produced nonsignificant differences in weight loss: mean (95% CI): -8 (-9, -7) versus -9 (-11, -8; P=0.21). RT+CR+AT and CR+AT had non-significantly differences in the reduction of body fat [-6.5 (-7.2, -5.8) versus -7.4 (-8.1, -6.7) kg] and skeletal muscle [-2.1 (-2.7, -1.5) versus -2.1 (-2.7, -1.4) kg] (P=0.20 and 0.23, respectively). RT+CR+AT produced significantly greater increases in leg muscle strength [4.9 (0.7, 9.0) versus -1.1 (-5.5, 3.2) Nm, P=0.05] and leg muscle quality [0.07 (0.03, 0.11) versus 0.02 (-0.02, 0.06) Nm/cm2, P=0.04]. Both RT+CR+AT and CR+AT produced significant improvements in VO2peak [108 (958, 157) versus 80 (30, 130) mL/min; P=0.001 and 0.002, respectively], and Kansas City Cardiomyopathy Questionnaire score [17 (12, 22) versus 23 (17, 28); P=0.001 for both], with no significant between-group differences. Both RT+CR+AT and CR+AT significantly reduced LV mass and arterial stiffness. There were no study-related serious adverse events. CONCLUSIONS: In older obese heart failure with preserved ejection fraction patients, CR+AT produces large improvements in VO2peak and quality-of-life. Adding RT to CR+AT increased leg strength and muscle quality without attenuating skeletal muscle loss or further increasing VO2peak or quality-of-life. REGISTRATION: URL: https://ClincalTrials.gov; Unique identifier: NCT02636439.