This study examined the effects of androgen suppression therapy (AST) on upper and lower body muscle strength and a range of direct measures of physical performance using a cross-sectional design with 118 men (48 men undertaking AST for prostate cancer and 70 healthy aged-matched controls) from a single tertiary center. Primary end points included muscle strength for the upper- and lower-body; functional performance--repeated chair rise, usual and fast 6-m walk, 6-m backwards walk and 400-m walk time; and dual-energy X-ray absorptiometry assessment--whole body, regional soft tissue composition and bone mineral density (BMD). Men on AST had significantly reduced muscle strength for the upper- and lower-body and impaired functional performance compared to controls (P<0.05). As expected, AST patients had significantly lower whole-body and hip BMD and higher percent of body fat than controls (P<0.05), and tended to have lower whole-body lean mass (-2.3 kg, P=0.077). Appendicular skeletal muscle was positively associated with upper-body (r=0.400-0.606, P<0.001) and lower-body (r=0.549-0.588, P<0.001) muscle strength, and strength was related to functional performance. Men undertaking AST were consistently impaired across a broad range of physical and functional musculoskeletal performance assessments compared with their age-matched normal controls. These findings are relevant for those patients considering AST for subclinical disease management, but whose physical reserve is marginal. Strategies to counter these adverse effects of AST need to be initiated so that independent living and quality of life can be maintained.