There is a causal relationship between diabetic foot ulceration, elevated plantar pressure, and severe sensory neuropathy. Cushioned footwear intended to relieve plantar pressure is well established for prevention and healing of plantar ulcers. The aim of the present study was to investigate whether pressure relief by means of a running shoe with optimized forefoot pressure damping is comparable to that of a custom-made soft insole placed into an in-depth shoe. The in-shoe pressures were compared to an in-depth shoe with the original cork insole and with a leather-soled Oxford shoe. The maximum reduction of plantar pressure in the running shoe was 47% under the 2nd and 3rd metatarsal heads, 29% at the first metatarsal head, and 32% at the great toe in comparison to the Oxford shoe. This was surpassed only by the custom-made insole, which reduced pressures at the metatarsal heads by 50%. The specially designed running shoe yielded the same pressure relief at the central metatarsal heads as the custom-made insole. Such shoes are likely to be very useful in preventing diabetic foot ulceration in high-risk patients as a comparatively affordable and immediately available device.