AIM: To evaluate the long-term safety and efficacy of vitrectomy and internal limiting membrane (ILM) peeling with or without gas tamponade for highly myopic foveoschisis. METHODS: We performed an open-label, observer-blinded clinical trial of 85 patients with myopic foveoschisis between 2000 and 2012. Patients were randomly allocated to one of two groups, those who received vitrectomy and ILM peeling without gas tamponade (no-gas group) or those who with gas tamponade (gas group) and follow up at least 5y. RESULTS: Visual acuity of gas group improved from 0.82±0.33 to 0.79±0.73 in 6mo, improved to 0.71±0.67 in 1y and within this range in the following 4y. Visual acuity of no-gas group improved from 0.81±0.46 to 0.78±0.66 in 6mo, improved to 0.70±0.65 in 1y. The finial visual acuity of two groups were significantly increased compared with the baseline (P<0.05). The visual acuity was improved in 35 of 40 eyes (87.5%) in gas group and 29 of 33 eyes (87.9%) in no-gas group, while there were no significant differences between gas group and no-gas group in the visual acuity. The foveoschisis on optical coherence tomography (OCT) completely resolved in 5 of 40 eyes in 1mo, 14 eyes in 6mo and 40 eyes in 1y in the gas group. While the foveoschisis completely resolved in 4 of 33 eyes in 1mo, 10 eyes in 6mo and 33 eyes in 1y in the no-gas group. CONCLUSION: Vitrectomy and ILM peeling without gas tamponade appears to be as effective in the treatment of myopic foveoschisis as vitrectomy and ILM with gas tamponade. However, eyes treated with no-gas tamponade showed more rapid resolution of myopic foveoschisis.