The purpose of this study was to evaluate whether an umbilical cord tissue graft (UCG) could promote reepithelialization in refractory cases of neurotrophic keratopathy, which failed traditional treatment modalities including amniotic membrane grafts. This retrospective case series included 3 eyes of 3 patients who underwent UCG placement for refractory stage 3 neurotrophic keratopathy. Records were reviewed to evaluate the clinical course including previous treatments, time to UCG dissolution, time to corneal epithelialization, and recurrence of epithelial defects. The time of a nonhealing epithelial defect before UCG placement ranged from 7.7 to 30 weeks (mean 21.0). UCG dissolution time ranged from 1.7 to 8.1 weeks (mean 5.0) compared with the previous failed amniotic membrane dissolution time of 0.3 to 1.6 weeks (mean 0.95). The time to complete epithelialization after UCG placement was 7.7 and 8.1 weeks, respectively, for the first 2 cases, whereas the third case did not fully epithelialize. Only 1 eye did not have recurrence of an epithelial defect. The maximum time of maintained epithelialization without recurrence ranged from 5 to 86 weeks (mean 42.7). Follow-up time was 37 to 108.1 weeks (mean 62.2) after first UCG placement. UCG may allow for longer retention time of tissue grafts, provide a mechanical barrier for protection, and aid in regeneration of the ocular surface. UCG may be an option for re-epithelialization in recalcitrant cases of neurotrophic keratopathy, after conventional treatments such as amniotic membrane grafts have failed.