Diabetes mellitus affects about one in 25 Australians. Neuropathic foot ulceration is a frequent complication in persons with diabetes. This study evaluates the importance of different risk factors for the development of this condition. The role of nonenzymatic glycosylation and pressure beneath the sole of the foot in the pathogenesis of neuropathic foot ulcers was investigated. Twenty-seven subjects with diabetes with a recent history of neuropathic foot ulceration were matched by age and sex with a group of 50 control subjects without neuropathy or history of foot ulceration. The degree of nonenzymatic glycosylation was assessed by analyzing the average level of glycosylated hemoglobin in the 3 years prior to the development of the foot ulcer and a goniometer assessment of peripheral joint (hand and ankle) flexibility. Dynamic pressure of the plantar aspect of the foot was recorded using a Musgrave Footprint System pedobarograph during a normal gait cycle. There was no significant difference in age, sex, body mass index, and duration or type of diabetes between the ulcer and control groups. The pressure of the plantar aspect of the foot was significantly elevated (p < 0.01). Ankle joint flexibility was reduced (p < 0.01) in cases with neuropathic foot ulceration compared with the control group. There was a trend toward elevation of glycosylated hemoglobin (HbA1c fraction) or HbA1c in the ulcer group (p = 0.06). The results suggested that nonenzymatic glycosylation occurs at a more significant level in patients with diabetes with a history of neuropathic foot ulceration.