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Background: To investigate anatomical and functional changes of the macula caused by epiretinal membrane (ERM) peeling procedures in patients with or without posterior vitreous detachment (PVD). Methods: This is a multicentric prospective observational study on thirty-seven (37) patients affected by symptomatic ERM who underwent 25-gauge pars plana vitrectomy (PPV), induction of a PVD (as needed) and peeling of both the internal limiting membrane (ILM) and ERM. Optical coherence tomography–angiography (OCT-A) (RS 3000, Nidek, Japan) and microperimetry (MP-3, Nidek, Japan) were performed; central retinal thickness (CRT), foveal avascular zone (FAZ) area and perimeter, vessel density and perfusion density, retinal sensitivity and fixation stability (as a total mean retinal sensitivity (MRS), and MRS in the ellipse area and bivariate contour ellipse area (BCEA)) were recorded at baseline and up to postoperative month 3. Results: Eyes were classified as having complete PVD (51.4%) or incomplete PVD (48.6%). At baseline, patients with incomplete PVD had worse best-corrected distance visual acuity (BCDVA), total MRS, MRS in the ellipse area and BCEA, and higher CRT than patients with complete PVD. At month 3, the differences in BCDVA between the two groups remained statistically significant, with patients with incomplete PVD having worse results (difference: 0.199 logMAR, p < 0.001). The difference in the MRS in the ellipse area was statistically significant at month 3 (−3.378 Db, p = 0.035), with greater improvement in patients with complete PVD. Conclusions: Our study shows that patients with incomplete PVD have worse conditions at baseline than patients with complete PVD, and the differences in visual acuity and retinal sensitivity were maintained postoperatively. [ABSTRACT FROM AUTHOR]