Nonhealing wounds along the fifth metatarsal associated with neuropathy and bone deformity frequently become complicated with osteomyelitis. Our surgical technique for complete fifth ray amputation with peroneal tendon transfer has been previously published. The present study evaluated the outcomes regarding success with initial healing and intermediate-term limb survival after this procedure, which is intended to resolve infection, remove bone deformity, heal and prevent recurrence of lateral column wounds, and maintain functional stability of the foot. An institutional review board-approved retrospective review of 21 consecutive cases was performed on patients who had undergone complete fifth ray amputation from August 2006 to September 2015. Comorbid conditions were assessed in relation to outcome. The typical stage 1 procedure involved complete fifth toe and metatarsal amputation, antibiotic bead placement, and preliminary wound closure. The stage 2 procedure was performed 2 weeks later and involved removal of the antibiotic beads, biopsy and remodeling of the cuboid, and peroneus longus tendon transfer to the cuboid. All cases involved ulceration along the fifth metatarsal. Of the 21 patients, 10 (47.6%) had undergone previous partial fifth ray amputation with recurrent ulceration at the residual metatarsal stump. Osteomyelitis of the fifth metatarsal was confirmed by bone culture and/or positive pathologic findings for osteomyelitis in 19 of 21 cases (90.5%). A total of 15 patients (71.4%) were completely healed at 10 weeks, and 10 patients (47.6%) required subsequent surgery, including 4 below-the-knee amputations and 1 Symes amputation. The average follow-up period was 37.0 (range 2.9 to 105) months. Despite the 10 patients (47.6%) requiring revision surgery, the limb salvage rate was 76.2% (16 of 21) at an average follow-up period of >3 years in this high-risk patient population.