There is evidence that appropriate footwear is an important factor in the prevention of foot pain in otherwise healthy people or foot ulcers in people with diabetes and peripheral neuropathy. A standard care for reducing forefoot plantar pressure is the utilization of orthotic devices such as total contact inserts (TCI) with therapeutic footwear. Most neuropathic ulcers occur under the metatarsal heads, and foot deformity combined with high localized plantar pressure, appear to be the most significant factors contributing to these ulcers. In this study, patient-specific finite element models of the second ray of the foot were developed to study the influence of TCI design on peak plantar pressure (PPP) under the metatarsal heads. A typical full contact insert was modified based on the results of finite element analyses, by inserting 4 mm diameter cylindrical plugs of softer material in the regions of high pressure. Validation of the numerical model was addressed by comparing the numerical results obtained by the finite element method with measured pressure distribution in the region of the metatarsal heads for a shoe and TCI condition. Two subjects, one with a history of forefoot pain and one with diabetes and peripheral neuropathy, were tested in the laboratory while wearing therapeutic shoes and customized inserts. The study showed that customized inserts with softer plugs distributed throughout the regions of high plantar pressure reduced the PPP over that of the TCI alone. This supports the outcome as predicted by the numerical model, without causing edge effects as reported by other investigators using different plug designs, and provides a greater degree of flexibility for customizing orthotic devices than current practice allows.