PURPOSE: This study examines the long-term clinical outcomes of an artificial endothelial replacement membrane implant used to treat corneal edema. It also explores the interaction between the device and the posterior surface of the cornea. METHODS: Patients suffering from late endothelial keratoplasty failure (5 patients) or bullous keratopathy (2 patients) after multiple surgeries underwent EndoArt (EyeYon Medical, Israel) implantation. Before surgery and at 1-, 3-, 6-, 12-, 18-, and 24-month intervals, corrected distance visual acuity and central corneal thickness were measured. High-resolution anterior segment optical coherence tomography images were analyzed at each interval to detect device detachment and evaluate the implant interaction with the corneal tissue over time. RESULTS: Corrected distance visual acuity improved from a mean of 1.32 ± 0.23 (logarithm of the Minimum Angle of Resolution) preoperatively to 0.95 ± 0.28 (logarithm of the Minimum Angle of Resolution) 2 years after surgery (P = 0.03). Central corneal thickness significantly decreased from 805 ± 131 μm preoperatively to 577 ± 90 μm postoperatively (P = 0.002). Four of the 7 patients experienced device detachment, requiring 1 or more rebubblings to achieve stable implant adhesion. Anterior segment optical coherence tomography showed annular fibrosis developing between the device margin and the host cornea in most patients, particularly those who had never experienced detachment. CONCLUSIONS: This study suggests that EndoArt is effective in the long term for improving corneal transparency and visual acuity in patients with chronic corneal edema with a limited prognosis for endothelial keratoplasty. The formation of fibrotic tissue between the periphery of the device and the host cornea may explain the strong adhesion of the implant.