AIM: To describe using spectral-domain optical coherence tomography the regeneration of the foveal morphology after pars plana (re)vitrectomy surgery and gas tamponade combined with injection of autologous platelet concentrate to treat full-thickness macular holes, and to describe different anatomical outcome. METHODS: A retrospective case series of 8 eyes of 8 patients was described. RESULTS: In all cases investigated, the platelet-assisted closure of macular holes was associated with a rapid resolution of cystic cavities in the foveal walls. In two patients, there was a regular regeneration of the foveal morphology after hole closure; the regenerated central fovea had a regular structure with a foveola and photoreceptors. In three other patients, there was an irregular regeneration of the fovea; a foveola was not formed, photoreceptor cells were absent from the foveal center, and the center was composed of Müller and retinal pigment epithelial (RPE) cells. The foveal regeneration after hole closure may proceed with or without a temporary detachment of the foveal center from the RPE, and with or without a direct contact between the central outer nuclear layer (ONL) and the RPE. Contacts between the ONL and RPE were observed only in patients with an irregular foveal regeneration after hole closure. CONCLUSION: The data show that there are different modes of foveal regeneration after closure of macular holes with (re)vitrectomy and platelet concentrate. It is suggested that the regular regeneration of the foveal morphology proceeds by Müller cell-mediated tissue movements without cell proliferation, whereas the irregular foveal regeneration proceeds in part by proliferation of Müller and RPE cells.