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To investigate the closure rate of primary full-thickness macular hole, following intraocular air tamponade combined with a nonsupine positioning regimen.A prospective study of patients with full-thickness macular hole, who underwent pars plana vitrectomy with internal limiting membrane peeling and intraocular air tamponade followed by 3 days of nonsupine positioning. Outcome measures were primary full-thickness macular hole closure and improvement in best-corrected visual acuity after 6 months.A total of 34 eyes were included. In the group of full-thickness macular hole ≤400 μm, primary closure occurred in 95% (19/20), whereas only 57% (8/14) of those >400 μm closed (P = 0.01). The mean gain in best-corrected visual acuity was 3.5 ETDRS (Early Treatment Diabetic Retinopathy Study) lines (SD = 1.5) (P < 0.01). The air bubble meniscus height at the first postoperative day was estimated to a mean of 59% (range, 50–70%), at the second postoperative day it was 46% (range, 40–55%), and the third day it was 39% (range, 30–45%). Mean intraocular air bubble duration was 10 days (range, 8–13 days).The combination of air tamponade and nonsupine positioning regimen leads to high closure rates for small/medium macular holes (≤400 μm), but not for large macular holes (>400 μm).