Context: Androgen deprivation therapy (ADT) used in the treatment of prostate cancer reduces bone mineral density (BMD) and predisposes to fractures. The structural basis of the BMD deficit and bone fragility is uncertain. Objective and Patients: We investigated changes in bone microarchitecture in 26 men (70.6 ± 6.8 yr) with nonmetastatic prostate cancer during the first year of ADT using the new technique of high-resolution peripheral quantitative computed tomography. Design and Setting: We conducted a 12-month prospective observational study in the setting of a tertiary referral center. Results: After 12 months of ADT, total volumetric density decreased by 5.2 ± 5.4% at the distal radius and 4.2 ± 2.7% at the distal tibia (both P < 0.001). This was due to a decrease in cortical volumetric BMD (by 11.3 ± 8.6% for radius and 6.0 ± 4.2% for tibia, all P < 0.001) and trabecular density (by 3.5 ± 6.0% for radius and 1.5 ± 2.3% for tibia, all P < 0.01), after correcting for trabecularization of cortical bone. Trabecular density decreased due to a decrease in trabecular number at both sites (P < 0.05). Total testosterone, but not estradiol, levels were independently associated with total and corrected cortical volumetric BMD at the tibia. Conclusions: Sex steroid deficiency induced by ADT for prostate cancer results in microarchitectural decay. Bone fragility in these men may be more closely linked to testosterone than estradiol deficiency.