Background Despite the constant refinement of techniques and surgical aids, extremely large and refractory macular holes continue to have poor surgical outcomes with the current standard of care. The objective of the present study is to assess the anatomical and functional outcomes, as well as the structural change through time, of the optical coherence tomography of patients with refractory macular holes treated with a full-thickness autologous retinal transplant. Methods Prospective, case series. We include patients with a clinical diagnosis of refractory macular holes with a minimum diameter of at least 500 µm. All the patients had a comprehensive ophthalmological examination, which included a best-corrected visual acuity assessment, fundus examination, and optical coherence analysis. All the patients underwent a 23-gauge pars plana vitrectomy with a full-thickness retinal transplant and silicone oil tamponade (5000 cs<). Follow-up was done at 1, 3, 6, and 12 months. Statistical analysis was done with a test for repeated measurements and Bonferroni correction, with an alpha value of 0.05 for statistical significance and a Mann-Whitney U test for nonparametric continuous variables. Results We enrolled 13 eyes from 13 patients (mean age: 67.15 years) with refractory macular holes, with a mean base diameter of 1615.38 ± 689.19 µm and a minimum diameter of 964.08 ± 709.77 µm. The closure rate after 12 months of follow-up was 76.92%. Six patients with a closed macular hole at the end of the follow-up had complete recovery of the myoid/ellipsoid layer. The remaining showed a 44.9% reduction of the initial gap. Most patients formed a pseudofovea and normalization of the internal retinal layers. Despite a positive trend toward visual recovery (p = 0.034), after the correction of the alpha value, the change lost its statistical significance. During follow-up, one patient developed mild proliferative vitreoretinopathy and epiretinal membrane without anatomical or functional consequences. Conclusions An autologous full-thickness retinal transplant may improve the anatomical and structural outcome of patients with refractory macular holes. The full safety profile of this new technique is still unknown. More studies are needed in order to assess functional changes through time.