Objectives: To describe the prevalence of lamellar hole-associated epiretinal proliferation (LHEP) and to correlate this finding with lamellar macular hole (LMH) morphology and prognosis after a surgical or conservative approach. Methods: This is a retrospective multicenter case series comprising consecutive LMH patients followed for ≥6 months. Serial spectral-domain optical coherence tomographies were evaluated for the presence of epiretinal membrane (ERM) and LHEP, diameter of the LMH aperture, base, and floor thickness. Pars plana vitrectomy with ERM and internal limiting membrane peeling was performed in the surgical cases. Results: A total of 62 eyes from 57 consecutive patients were included. Mean follow-up time was 27.1 ± 19.8 months. LHEP was observed in 33 (53.2%) eyes. Patients with LMH and LHEP presented a larger external diameter (p = 0.001) and thinner floors (p = 0.018). Twenty-seven (81.8%) of the patients with LMH and LHEP presented a degenerative intraretinal cavitation, compared to 23.3% in the non-LHEP group (p = 0.001). No differences were observed in visual performance or closure rate between the 2 groups after surgery or in the subset of patients followed conservatively. Conclusions: LHEP was correlated with the anatomical conformation of the LMH, yielding thinner floors and larger external diameters. However, it did not correlate with the anatomical or functional results, both in the patients who underwent surgery and in those managed conservatively.