Objective: Patients with diabetes mellitus (DM) and a transmetatarsal amputation (TMA) have considerable deficits in function compared with age- matched controls. The purpose of this study was to determine if therapeutic footwear could improve the functional mobility of patients with DM and TMA. Study Design: Repeated-measures design. Setting: Academic medical center. Patients: Thirty subjects (10 women, 20 men) with DM and a TMA, with a mean age of 61.7 ± 4.0yrs. Interventions: Six types of footwear evaluating the following components: length of shoe (full-length or short shoe), a rigid rocker-bottom sole, and an ankle-foot-orthosis. Outcome Measures: Physical Performance Test (PPT), functional reach, and walking speed. Measurements in each footwear condition occurred after a 1-month adjustment period. Results: Patients wearing full-length custom-made shoes with a total-contact insert, a rigid rocker-bottom sole or a short shoe with a rigid rocker-bottom sole (with or without an ankle-foot-orthosis) had similar and significantly higher scores in the Plat and faster walking speed than when wearing regular shoes with a toe filler (p < .05). The short shoe and the ankle-foot-orthosis, however, generated many patient complaints about cosmesis and restriction at the ankle, respectively. There were no differences in any of the measures of functional reach. Conclusion: Although there are individual exceptions, we recommend the full-length shoe, total-contact insert, and a rigid rocker- bottom sole for most patients with DM and a TMA.