Abstract PURPOSE: To determine the effectiveness of removal of the internal limiting membrane in the treatment of full-thickness macular holes. METHODS: Data were reviewed from a prospective study on 47 consecutive eyes with full-thickness macular holes undergoing vitrectomy, internal limiting membrane maculorhexis, and fluid-gas exchange. No eye underwent repeat macular hole surgery. A meta-analysis was performed to compare the outcomes of different surgical techniques in the treatment of full-thickness macular holes. RESULTS: The outcome measures were disappearance of the submacular fluid and the change in best-corrected visual acuity. The surgery was anatomically successful in 44 of the 46 eyes (96%) and 39 of the eyes (85%) showed an improvement of at least two Snellen lines. Best-corrected final vision was 20/40 in 18 (39%) eyes. No permanent complications specifically caused by the removal of the macular internal limiting membrane were detected; the minor hemorrhages and retinal edema seen in most eyes resolved spontaneously. Retinal detachment developed and was successfully treated in three eyes (7%). A meta-analysis on 1,654 eyes from published reports showed that internal limiting membrane maculorhexis appears to significantly ( P < .0001) increase the anatomical and functional success rates in macular hole surgery. CONCLUSIONS: Internal limiting membrane removal is an important development in the evolving field of macular hole surgery. A randomized, prospective, multicenter clinical trial should be performed to determine which surgical technique is the most beneficial in patients with full-thickness macular holes.