Purpose <p>The aim of this study was to evaluate the outcome and complications associated with pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling in the treatment of macular edema of various etiologies.</p> Methods <p>This observational, multicenter, longitudinal, retrospective study, initiated by the Société Française de Chirurgie Rétino-Vitréene in 2022, involved 27 surgeons from all over France. Data were collected preoperatively and at multiple postoperative time periods up to two years. The etiologies of macular edema included epiretinal membrane (ERM), vitreomacular traction syndrome (VMT), diabetic macular edema (DME), retinal vein occlusion (RVO), and postsurgical cystoid macular edema (PCME).</p> Results <p>A total of 876 patients were included in the study. Best-corrected visual acuity (BCVA) significantly improved from 0.44 ± 0.26logMAR preoperatively to 0.22 ± 0.33logMAR at 1–2&#xa0;years postoperatively (<i>p</i> &lt; 0.001). Central macular thickness decreased from 422 ± 97&#xa0;μm preoperatively to 337 ± 67&#xa0;μm at 1–2&#xa0;years. Intraoperative complications included retinal tear or retinal detachment in 6.3% of cases and intravitreal hemorrhage in 0.6% of cases. Postoperative retinal detachment occurred in 3.2% of patients. Intravitreal injection preoperatively was associated with poorer BCVA outcomes in the follow-up (<i>p</i> &lt; 0.001). Patients who attained the best BCVA postoperatively demonstrated a macular thickness ranging from 320 to 400&#xa0;μm.</p> Conclusion <p>PPV with ILM peeling proved to be an effective treatment for macular edema across various etiologies. Interestingly, good visual acuity following ILM peeling appeared to be associated with a larger macular thickness compared to the normal population. Intravitreal injections of anti-VEGF or dexamethasone implant preoperatively seemed to limit visual recovery.</p>