Lower-extremity amputation in patients with diabetes is associated with premature mortality and impaired ambulatory status. Despite advances in limb salvage techniques, certain patients will require major amputation. The hypothesis of this study is that self-reported outcomes of patients with non-reconstructable Charcot neuroarthropathy and chronic osteomyelitis improve after trans-tibial amputation. Self-reported outcome was assessed using the Medical Outcome Study Short Form 36-item health survey (SF-36) and the Foot and Ankle Ability Measure. The study group included 13 patients with diabetes who underwent a trans-tibial amputation and completed both the Medical Outcome Study SF-36 and the Foot and Ankle Measure pre- and post-operatively. Significant improvement after trans-tibial amputation occurred in the SF-36 Physical Component Summary score and both the Foot and Ankle Measure Activity of Daily Living and Sports scores at a mean follow-up of 79weeks (range 53-122weeks). Although the SF-36 Mental Component Summary score improved, the improvement did not achieve statistical significance (P=0.30). Twelve of the 13 patients were satisfied with the amputation and had no reservations. In a select group of Charcot neuroarthropathy patients with chronic osteomyelitis, trans-tibial amputation resulted in improvement in self-reported outcomes. Although major lower-extremity amputation is a devastating complication in patients with diabetes, the results of this study provides some evidence for optimism in these high-risk patients.