Purpose <p>To evaluate the role of intraoperative display of pre-operative digital enface optical coherence tomography (OCT) in guiding the epiretinal membrane (ERM) peeling, without vital dye staining.</p> Methods <p>In this prospective interventional study, patients undergoing ERM/inner limiting membrane (ILM) peeling were included. Structural OCT, enface and OCT Angiography (OCTA) were pre-operatively collected. The most suitable point to start the peeling was identified as a hyporeflective area on enface nearby the area of greater adhesion of the ERM. Pre-operative OCTA and enface were shown intraoperatively as a topographic map to identify the selected point. Dyes were not used intraoperatively, unless ILM was still evident by intraoperative OCT or in doubtful cases.</p> Results <p>Thirty eyes were included. In all cases, the identified enface area resulted suitable to create the peel flap at the first attempt without staining. In 14 eyes, the ERM/ILM were peeled simultaneously, in 7 eyes only part of the ILM was peeled with ERM. The ERM showed high grade of adherence in 11 out of 14 cases of simultaneous peeling. Greater ERM adherence correlated with increased likelihood of simultaneous peeling. A significant positive association between ERM stage and adhesion grade was evident with a moderate-to-strong monotonic relationship.</p> Conclusions <p>The intraoperative display of preoperative digital enface OCT proved feasible for identifying a suitable site for ERM flap initiation. Greater ERM adhesion was significantly associated with the intraoperative occurrence of simultaneous ERM/ILM peeling, suggesting that ERM adhesion may represent a potential imaging biomarker that warrants validation in larger prospective studies.</p>