Despite increasing interest in age- and gender-related bone alterations, data on trabecular microstructure at the proximal tibia are scarce. The aim of this study was to identify trabecular microstructural change at the human proximal tibia with age and gender, using micro-computed tomography (micro-CT) and scanning electron microscopy (SEM). Fifty-six proximal tibias from 28 Japanese men and women (57-98 years of age) were used in this study. The subjects were chosen to give an even age and gender distribution. Both women and men were divided into three age groups, middle (57-68 years), old (72-82 years) and elderly (87-98 years) groups. The trabecular bone specimens from the medial compartment of the proximal tibial metaphysis were examined. Trabecular bone mineral density (BMD), bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) decreased between the middle-aged and elderly groups similarly in women and men. However, trabecular number (Tb.N) decreased by 13% between the middle-aged and elderly groups in women and nearly double that in men. As compared with women, men had higher BV/TV and lower trabecular separation (Tb.Sp) in the old age and elderly groups, and higher Tb.N and connectivity density (Conn.D) in the elderly group. Increased trabecular resorbing surfaces, perforated or disconnected trabeculae and microcallus formations were observed with age. These findings indicate that both BMD and BV/TV decreased at the proximal tibia with age similarly for women and men, but significant differences between women and men were observed for some microstructural parameters. These findings illustrate potential mechanisms underlying osteoporotic proximal tibial fracture.