OBJECTIVE -To investigate the relationship among plantar foot pressure, plantar subcutaneous tissue thickness, severity of neuropathy (vibration perception threshold [VPT]), callus, and BMI in a large group of neuropathic diabetic patients at risk of foot ulceration. RESEARCH DESIGN AND METHODS-A total of 157 diabetic neuropathic patients (VPT Ͼ25 V) without either peripheral vascular or ulcer history were studied. Plantar foot pressure and plantar tissue thickness were measured at each metatarsal head (MTH) using an optical pedobarograph and an ultrasound scanning platform, respectively.RESULTS -A significant association was observed between peak plantar pressure and plantar tissue thickness at all MTHs (Ϫ0.26 Ͻ r Ͻ Ϫ0.61, P Ͻ 0.0001), with the least pronounced association at the first MTH. In addition, the pressure time integral was significantly associated with plantar tissue thickness (Ϫ0.24 Ͻ r Ͻ Ϫ0.57, P Ͻ 0.0001). BMI was significantly related to plantar tissue thickness (0.18 Ͻ r Ͻ 0.45, P Ͻ 0.05), but not to peak forefoot pressures. Subjects with callus had significantly reduced plantar tissue thickness at all MTHs except the first MTH and increased peak pressures at all MTHs (P Ͻ 0.001).CONCLUSIONS -This study confirms a strong inverse relationship between plantar tissue thickness and dynamic foot pressure measurements. Long-term follow-up of this patient population will confirm whether reduced plantar tissue thickness predicts the development of diabetic foot ulcers.