To compare the efficacy of air and perfluoropropane (C3F8) with pars plana vitrectomy (PPV) in highly myopic macular holes (HMMH), and explore the factors related to surgical prognosis.A retrospective comparison of a consecutive series of HMMHs undergone PPV and internal limiting membrane (ILM) peeling. According to tamponade type, they were divided into air group and C3F8 group, which were further divided into subgroups based on hole diameter or axial length (AXL). Anatomical and functional outcome were compared between tamponades. Related factors of initial closure rate and postoperative best-corrected visual acuity (BCVA) were analyzed by logistic regression.The baseline characteristics in air group (n=63) and C3F8 group (n=37) were similar except the age of air was older (P=0.019). The mean follow-up period was 17.16 ± 17.97 months. After surgery, the initial closure rate of air group was 85.7% and that of C3F8 group was 83.7% (P=0.780). And the initial closure rate showed no difference between tamponades in the same subgroup classified by hole diameter or AXL (All P>0.05). Postoperative BCVA improved significantly in both groups (P<0.001), but no difference between them (P=0.793). Logistic regression showed age, MLD and AXL were risk factors of initial closure rate, and preoperative BCVA was the only factor associated with postoperative BCVA (all P<0.05).With a long-term follow-up of HMMH, we found air had a similar tamponade effect anatomically and functionally compared with C3F8. Air may also be a good choice for patients with HMMH.