Background: Androgen deprivation therapy (ADT) in the management of prostate cancer (PCa) results in an array of adverse effects, and exercise is one strategy to counter treatment-related musculoskeletal toxicities. This study assessed the prevalence of exercise responsiveness in men with PCa undergoing ADT in terms of body composition, muscle strength, and physical function. Methods: Prospective analyses were performed in 152 men (aged 43–90 years) with PCa receiving ADT who were engaged in resistance exercise combined with aerobic or impact training for 3 to 6 months. Whole-body lean mass and fat mass (FM), trunk FM, and appendicular skeletal muscle were assessed with dual x-ray absorptiometry; upper and lower body muscle strength were assessed with the one-repetition maximum; and physical function was assessed with a battery of tests (6-m usual, fast, and backward walk; 400-m walk; repeated chair rise; stair climb). Results: Significant improvements were seen (P<.01) in lean mass (0.4±1.4 kg [range, −2.8 to +4.1 kg]), appendicular skeletal muscle (0.2±0.8 kg [range, −1.9 to +1.9 kg]), and all measures of muscle strength (chest press, 2.9±5.8 kg [range, −12.5 to +37.5 kg]; leg press, 29.2±27.6 kg [range, −50.0 to +140.0 kg]) and physical function (from −0.1±0.5 s [range, +1.3 to −2.1 s] for the 6-m walk; to −8.6±15.2 s [range, +25.2 to −69.7 s] for the 400-m walk). An increase in FM was also noted (0.6±1.8 kg [range, −3.6 to +7.3 kg]; P<.01). A total of 21 men did not exhibit a favorable response in at least one body composition component, 10 did not experience improved muscle strength, and 2 did not have improved physical function. However, all patients responded in at least one of the areas, and 120 (79%) favorably responded in all 3 areas. Conclusions: Despite considerable heterogeneity, most men with PCa receiving ADT responded to resistance-based multimodal exercise, and therefore our findings indicate that this form of exercise can be confidently prescribed to produce beneficial effects during active treatment.