Elevated stresses in deep plantar tissue of diabetic neuropathic patients were associated with an increased risk for foot ulceration, but only interfacial foot pressures are currently measured to evaluate susceptibility to ulcers. The goals of this study were to develop a real-time patient-specific plantar tissue stress monitor based on the Hertz contact theory. The biomechanical model for stress calculations considers the heel and metatarsal head pads, where most ulcers occur. For calculating stress concentrations around the bone-pad interface, plantar tissue is idealized as elastic and incompressible semi-infinite bulk (with properties measured by indentation), which is penetrated by a rigid sphere with the bone’s radius of curvature (from X-ray). Hertz’s theory is used to solve the bone-pad mechanical interactions, after introducing correction coefficients to consider large deformations. Foot-shoe forces are measured to solve and display the principal compressive, tensile, and von Mises plantar tissue stresses in real time. Our system can be miniaturized in a handheld computer, allowing plantar stress monitoring in the patient’s natural environment. Small groups of healthy subjects and diabetic patients participated in an evaluation study in which the differences between free walking and treadmill walking were examined. We also compared gait on a flat surface to gait on an ascending/descending slope of and when ascending/descending stairs. Peak internal compression stress was about threefold greater than the interface pressure at the calcaneus region. Subjects who were inexperience in treadmill walking displayed high gait-cycle variability in the internal stresses as well as poor foot loading. There was no statistical difference between gait on a flat surface and gait when ascending/descending a slope. Internal stresses under the calcaneus during gait on a flat surface, however, were significantly higher than when ascending/descending stairs. We conclude that the present stress monitor is a promising tool for real-time patient-specific evaluation of deep tissue stresses, providing valuable information in the effort to protect diabetic patients from foot ulceration. Clinical studies are now underway to identify which stress parameters can distinguish between diabetic and normal subjects; these parameters may be used for establishing injury threshold criteria.