To report the structural and functional outcomes of autologous neurosensory retinal transplant for closure of refractory large macular holes (MHs). Multicenter, retrospective, consecutive case series. A total of 41 eyes of 41 patients with a full-thickness MH refractory to prior vitrectomy with internal limiting membrane (ILM) peel and tamponade. All patients underwent pars plana vitrectomy, autologous neurosensory retinal transplant with gas, silicone oil tamponade, or short-term perfluoro-n-octane heavy-liquid tamponade. All patients had at least 6 months' follow-up. Anatomic closure of MH, change in ellipsoid zone (EZ) and external limiting membrane (ELM) defect on OCT, visual acuity (VA) recovery, and surgical complications were analyzed. Mean number of prior surgeries was 1.5±0.94 (range, 1-3), and patients were followed for a mean of 11.1±7.7 months (range, 6-36 months). Complete anatomic closure of MH by OCT was achieved in 36 of 41 eyes (87.8%). Mean corrected VA (logarithm of the minimum angle of resolution [logMAR]) improved (P = 0.03) from 1.11±0.66 (range, 0.48-3) to 1.03±0.51 (range, 0.1-2) at the last postoperative visit. The VA improved (≥0.3 logMAR units) in 15 eyes (36.6%), was stable in 17 eyes (41.5%), and worsened in 9 eyes (21.9%). Among eyes with anatomic closure, VA improved in 52.3% and worsened in 13.8%, whereas in those without closure, VA worsened in 40% and improved in none. Mean preoperative largest basal diameter was 1468.1±656.4 μm (range, 621-2600 μm), and mean inner-opening diameter was 825±422.5 μm (range, 336-1649 μm). Mean preoperative EZ defect was 1777.3±513.8 μm (range, 963-2808 μm), which decreased to 1370±556.9 μm (range, 288-2000 μm) at final follow-up (P = 0.007). Mean preoperative ELM was 1681.5±429 μm (range, 1172-2606 μm), which decreased to 1408.5±571.2 μm (range, 200-2000 μm) at final follow-up (P = 0.017). Major postoperative complications were retinal detachment (n = 1) and vitreous hemorrhage (n = 1). There were no cases of proliferative vitreoretinopathy, endophthalmitis, suprachoroidal hemorrhage, or choroidal neovascularization. The autologous retinal transplant technique offers a high degree of anatomic success and proved safe in this initial experience for closure of refractory MHs.