AIM: To evaluate whether fluid-air exchange is an effective treatment for unclosed macular hole (MH) after primary vitrectomy. METHODS: This retrospective study included patients with an unclosed MH within 1–2wk after vitrectomy. Patients were divided into the vitrectomy, fluid-air exchange, and observation groups according to the secondary treatment. The anatomical outcomes and postoperative visual acuity were recorded. RESULTS: The analysis included 25 eyes in 25 patients (16 females) aged 37–74y (vitrectomy group, n=10; fluid-air exchange group, n=9; observation group, n=6). Closure rate after secondary treatment was 100% in the vitrectomy group, 88.9% in the fluid-air exchange group and 33.3% in the observation group. Optical coherence tomography images obtained at the last follow-up revealed that continuity of the external limiting membrane (ELM) was significantly more common (P=0.004) in the fluid-air group (8/9 eyes, 88.9%) than in the vitrectomy group (2/10 eyes, 20.0%) and that macular morphology was better in the fluid-air group than in the vitrectomy group. No serious complications were observed after secondary treatment. CONCLUSION: Fluid-air exchange is an alternative option to repeat vitrectomy for patients with an unclosed MH after initial vitrectomy with elevated macular edge.