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The inverted flap (IF) technique has recently been introduced in macular hole (MH) surgery. The IF technique has shown an increase of the success rate in the case of large MHs and in MHs associated with high myopia. This study reports the anatomical and functional results in a large series of patients affected by MH treated using pars plana vitrectomy and gas tamponade combined with internal limiting membrane (ILM) peeling or IF.This is a retrospective, consecutive, nonrandomized comparative study of patients affected by idiopathic or myopic MH treated using small-gauge pars plana vitrectomy (25- or 23-gauge) between January 2011 and May 2016. The patients were divided into two groups according to the ILM removal technique (complete removal vs. IF). A subgroup analysis was performed according to the MH diameter (MH < 400 µm and MH ≥ 400 µm), axial length (AL < 26 mm and AL ≥ 26 mm), and the presence of chorioretinal atrophy in the macular area (present or absent).We included 620 eyes of 570 patients affected by an MH, 300 patients underwent pars plana vitrectomy and ILM peeling and 320 patients underwent pars plana vitrectomy and IF. Overall, 84.94% of the patients had complete anatomical success characterized by MH closure after the operation. In particular, among the patients who underwent only ILM peeling the closure rate was 78.75%; among the patients who underwent the IF technique, it was 91.93% (P = 0.001); and among the patients affected by full-thickness MH ≥400 µm, success was achieved in 95.6% of the cases in the IF group and in 78.6% in the ILM peeling group (P = 0.001); among the patients with an axial length ≥26 mm, success was achieved in 88.4% of the cases in the IF group and in 38.9% in the ILM peeling group (P = 0.001). Average preoperative best-corrected visual acuity was 0.77 (SD = 0.32) logarithm of the minimum angle of resolution (20/118 Snellen) in the peeling group and 0.74 (SD = 0.33) logarithm of the minimum angle of resolution (20/110 Snellen) in the IF group (P = 0.31). Mean postoperative best-corrected visual acuity was 0.52 (SD = 0.42) logarithm of the minimum angle of resolution (20/66 Snellen) in the peeling group and 0.43 (SD = 0.31) logarithm of the minimum angle of resolution (20/53 Snellen) in the IF group (P = 0.003).Vitrectomy associated with the inverted ILM flap technique seems to be effective surgery for idiopathic and myopic large MHs, improving both functional and anatomical outcomes.