Current practice in the prevention of recurrence of neuropathic foot ulcers is to prescribe accommodative in-shoe orthoses or insoles which reduce plantar pressure levels at locations of bony prominences, particularly under the metatarsal heads. To date, design of these orthoses has largely been a trial and error process. There is little quantitative information available regarding the effects of thickness and the influence of soft tissue characteristics on the cushioning effect of such interventions. The current paper investigated alterations in pressure under the second metatarsal head as a function of insole thickness and tissue thickness. Both experimental and quasi-static plane strain finite element approaches were employed. The orthoses chosen reduced plantar pressure by a maximum of approximately 30% and were more effective (on a percentage basis) in the setting of reduced sub-metatarsal tissue thickness. Peak normal stresses predicted by the FE models were, on average, within 5.9% of experimentally measured values for the normal tissue case and 8.1% for the reduced tissue case. The techniques presented represent a promising approach to understanding plantar cushioning and the principles involved in the design of therapeutic footwear for insensate feet.