BACKGROUND A comprehensive understanding of clinical risk factors for developing foot ulcerations would help clinicians to categorize patients by their risk status and schedule intervention resources accordingly to prevent amputation. OBJECTIVE To evaluate risk factors for foot ulcerations among persons with diabetes mellitus. METHODS We enrolled 225 age-matched patients, 46.7% male, with a ratio of approximately 1:2 cases: controls (76 case-patients and 149 control subjects). Case-patients were defined as subjects who met the enrollment criteria and who had an existing foot ulceration or a recent history of a foot ulceration. Control subjects were defined as subjects with no history of foot ulceration. A stepwise logistic regression model was used for analysis. RESULTS An elevated plantar pressure (> 65 N/cm2), history of amputation, lengthy duration of diabetes (> 10 years), foot deformities (hallux rigidus or hammer toes), male sex, poor diabetes control (glycosylated hemoglobin > 9%), 1 or more subjective symptoms of neuropathy, and an elevated vibration perception threshold (> 25 V) were significantly associated with foot ulceration. In addition, 59 patients (78%) with ulceration had a rigid deformity directly associated with the site of ulceration. No significant associations were noted between vascular disease, level of formal education, nephropathy, retinopathy, impaired vision, or obesity and foot ulceration on multivariate analysis. CONCLUSIONS Neuropathy, foot deformity, high plantar pressures, and a history of amputation are significantly associated with the presence of foot ulceration. Although vascular and renal disease may result in delayed wound healing and subsequent amputation, they are not significant risk factors for the development of diabetic foot ulceration.