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Prostate cancer is the most common cancer in men, and patients treated with androgen deprivation therapy (ADT) experience unfavorable changes in body composition and associated metabolic complications, which can increase the risk of cardiovascular disease. We examined the effect of a 6-month program of aerobic and resistance exercise aimed at improving body composition and cardiorespiratory health in this population.Ninety-seven men (43–90 yr) with localized prostate cancer receiving ADT were randomized to either exercise (EX, n = 50) or usual care (CON, n = 47). Supervised exercise was undertaken twice weekly at moderate to high intensity. Measures of cardiorespiratory capacity (V˙O2max), resting metabolic rate, central blood pressure, hemodynamic variables, blood markers, and body composition were assessed.There was a significant group–time interaction present for V˙O2max (P = 0.033) with a treatment effect for EX of 0.11 L·min−1 (95% confidence interval [CI] = 0.04–0.19) (relative to body mass = 1.3 mL·kg−1·min−1, 95% CI = 0.3–2.3) and fat oxidation (P = 0.037) of 12.0 mg·min−1 (95% CI = 2.3–21.7). Similarly, there was a significant improvement in glucose (P < 0.001) for EX of −0.5 mmol·L−1 (95% CI = −0.8 to −0.3), with no change in prostate-specific antigen or testosterone as a result of exercise. Body composition was enhanced for EX with adjusted mean differences in lean mass (P = 0.015) of 0.8 kg (95% CI = 0.3–1.3), total fat mass (P = 0.020) of −1.1 kg (95% CI = −1.8 to −0.5), and trunk fat mass (P < 0.001) of −1.0 kg (95% CI = −1.4 to −0.6).A 6-month combined aerobic and resistance exercise program has a significant favorable effect on cardiorespiratory capacity, resting fat oxidation, glucose, and body composition despite the adverse effects of hormone suppression. Combined aerobic and resistance training should be considered a key adjuvant component in men undergoing ADT for the treatment of prostate cancer.