AIM:To investigate the efficacy and safety of different fillers combined with vitrectomy and internal limiting membrane stripping in the treatment of idiopathic macular hole(IMH).METHODS: This retrospective study included 117 patients(117 eyes)with IMH who were admitted to the department of ophthalmology in the hospital between July 2018 and March 2020. Both groups were treated with vitrectomy combined with internal limiting membrane stripping. Sixty-five patients(65 eyes)receiving air filling were included in the air group, while 52 cases(52 eyes)receiving C3F8 filling were included in the C3F8 group. Re-examination was performed before operation and at 1, 2, and 3mo after operation. The rate of hole closure, closed shape, visual acuity, central macular thickness(CRT), exterior limiting membrane(ELM)defect diameter, ellipsoid band defect diameter, intraocular pressure, and the incidence of postoperative complications at the last follow-up were counted. RESULTS: The postoperative air absorption time of air group and C3F8 group was 8.55±2.17d and 25.74±7.41d, respectively(P<0.05). The macular hole closure rates in air group and C3F8 group were 95.4% and 98.1%, respectively(P>0.05). There were no significant differences in the proportions of different shapes of closed holes between the two groups(P>0.05). Visual acuity of the two groups was significantly improved at 3mo after operation(P<0.001). There were no significant differences in LogMAR visual acuity and visual acuity changes between air group and C3F8 group(P>0.05). The CRT was increased significantly after operation(P<0.001), and the diameters of ELM defect and ellipsoid band defect were reduced(P<0.001). There were no significant differences in above indicators between the two groups(P>0.05). There was no significant difference in intraocular pressure between the two groups before and after treatment(P>0.05). No serious complications were observed in the two groups. CONCLUSION: Vitrectomy and internal limiting membrane stripping combined with air filling and C3F8 filling are effective and safe in the treatment of IMH. Clinically, the operation mode can be selected according to the actual situation.