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Foot pain and lower-limb neuroischemia in diabetes mellitus is common and can be debilitating and difficult to treat. We report a comparison of orthotic materials to manage foot pain in a 59-year-old man with type 1 diabetes mellitus, peripheral neuropathy, peripheral arterial disease, and a history of foot ulceration. We investigated a range of in-shoe foot orthoses for comfort and plantar pressure reduction in a cross-sectional study. The most comfortable and most effective pressure-reducing orthoses were subsequently evaluated for pain relief in a single system alternating-treatment design. After 9 weeks, foot pain was completely resolved with customized multidensity foot orthoses. The outcome of this case study suggests that customized multidensity foot orthoses may be a useful intervention to reduce foot pain and maintain function in the neuroischemic diabetic foot. (J Am Podiatr Med Assoc 98(2): 143–148, 2008)