AIM: To report the surgical technique and efficacy of the tiled transplantation internal limiting membrane (ILM) pedicle flap technique after vitrectomy for 33 patients with large macular hole (MH). METHODS: This study was a prospective noncontrolled interventional study. All patients were treated by vitrectomy, the tiled transplantation ILM pedicle flap and gas tamponade. All patients underwent visual acuity measurements and optical coherence tomography (OCT), during preoperative and the follow-up visits postoperative. RESULTS: Two high-myopic patient had flap dislocation during surgery. The thorough closure of MH following the tiled transplantation ILM pedicle flap technique was ultimately achieved in 31 patients observed by OCT imaging (93.94%) 1wk after surgery. Visual acuity improved from 1.51±0.31 (logMAR) preoperative to 0.92±0.30 6mo after surgery (P=0.000). There were no significant changes in OCT finding during the follow-up period from 1mo to 6mo after surgery. CONCLUSION: The tiled transplantation ILM pedicle flap technique provides bridge for retinal gliosis to achieve successful closures of the large MHs, and the microenvironment of this technique is more similar to the normal physiological conditions.