Objective:To analyze the effect of vitrectomy combined with internal limiting membrane (ILM) peeling on the prevention of post-vitrectomy epiretinal membrane (ERM) in macular-off rhegmatogenous retinal detachment (RRD) and its influence on visual outcomes.Methods:A cohort study was conducted.Seventy-four patients (74 eyes) with macular-off RRD, who realized retinal reattachment after vitrectomy and silicone oil tamponade from January 2015 to January 2018 in Baoding NO.1 Central Hospital, were enrolled.The patients were divided into the non-ILM peeling group (36 cases, 36 eyes) and ILM peeling group (38 cases, 38 eyes) according to whether they received ILM peeling or not.The patients underwent silicone oil removal within 3 to 5 months after the surgery.Best corrected visual acuity (BCVA), slit-lamp microscopy, indirect ophthalmoscopy, fundus photography and optical coherence tomography (OCT) were examined before and at 1, 6 and 12 months after the surgery.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Baoding NO.1 Central Hospital (No.[2019]042). Written informed consent was obtained from each patient.Results:There was no ERM found in the two groups at 1 month after the operation.There were 3 eyes (8.33%) with ERM in the non-ILM peeling group and 2 eyes (5.26%) in the ILM peeling group at 6 months after the operation, with no statistically significant difference between them ( P=0.067). There were 9 eyes (25.00%) with ERM in the non-ILM peeling group and 4 eyes (10.53%) in the ILM peeling group at 12 months postoperatively, with no statistically significant difference between them ( χ2=2.674, P=0.102). There was a significant difference in BCVA between before and after the operation in the two groups ( Ftime=31.692, P<0.001). Postoperative 1-, 6-and 12-month BCVA were all significantly better than the preoperative BCVA in the two groups (all at P<0.05). There was no significant difference in BCVA between the two groups ( Fgroup=0.117, P=0.773). OCT images showed that there were 25 eyes (77.78%) and 30 eyes (78.95%) with the intact ellipsoid zone in the non-ILM peeling group and ILM peeling group at 12 months after the operation, respectively, with no statistically significant difference between them ( χ2=0.875, P=0.350). Conclusions:Compared with vitrectomy alone, the vitrectomy combined with ILM peeling does not show better efficacy in the prevention of ERM occurrence in macula-off RRD patients and has no obvious influence on postoperative visual acuity.