Aims. Androgen deprivation therapy (ADT) for the management of prostate cancer is associated with a range of musculoskeletal toxicities. Although exercise with rehabilitative intent is effective in reversing a number of these adverse effects, it is unknown if exercise simultaneously initiated with ADT can prevent toxicities from occurring. The purpose of this study was to determine if exercise can mitigate these adverse effects in men during the initial phase of testosterone deprivation. Methods. Fifty-one men initiating ADT for prostate cancer were randomized to exercise (EX, n = 26) or usual care (CON, n = 25) for 6 months. Exercise consisted of progressive resistance, aerobic, and impact-loading exercise 3 times per week at moderate-to-high intensity under supervision. Whole body lean mass and bone mineral content (BMC), and total hip and lumbar spine bone mineral density (BMD) were assessed by DXA. Neuromuscular strength for chest press, seated row and leg press exercises were assessed using the 1RM method. Results. There was a significant difference between groups following 6 months for whole body lean mass (p = 0.023) being preserved in EX and decreasing in CON by 1.15 kg. Similarly, there were significant between group differences for all strength measures (p < 0.01) with chest press strength preserved and leg press (33.3%) and seated row strength (7.8%) increased in EX, while chest press decreased (-7.5%) and leg press strength increased (9.6%) in CON. There was no significant change in EX or CON for whole body BMC or spine BMD with hip BMD decreasing in CON by -1.2% (p=0.019). Conclusions. Lean mass and bone mass can be preserved and strength improved in men who simultaneously initiate exercise and ADT. Consequently, men initiating ADT should be encouraged to undertake specific exercise as an adjunct treatment to preserve their musculoskeletal health.