To explore the impact of intracameral air tamponade pressure and duration on graft attachment and rebubbling rates.A prospective, interventional, nonrandomized study.setting: Department of Ophthalmology, Charité – Universitätsmedizin Berlin. study population: One hundred seventeen patients who underwent Descemet membrane endothelial keratoplasty (DMEK). observation: Intraocular pressure (IOP) at the end of the surgery, immediately after filling the anterior chamber with air, categorized into low (<10 mm Hg), normal (10–20 mm Hg), and high (>20 mm Hg), and the time until partial removal of the air. main outcome measures: Rebubbling rates and endothelial cell density over a 3-month follow-up period analyzed by a multivariable Cox regression model and an analysis of covariance model.Thirty-two patients required a rebubbling (27% [95% CI 19%–35%]). Nine patients required more than 1 rebubbling (7% [95% CI 3%–12%]). Compared with normal IOP, lower (HR 8.98 [95% CI 1.07–75.41]) and higher IOP (HR 10.63 [95% CI 1.44–78.27]) increased the risk of requiring a rebubbling (P = .006). Independent of the IOP, an air tamponade duration beyond 2 hours reduced the risk of rebubbling (HR 0.36 [95% CI 0.18–0.71, P = .003]). One month after surgery, the mean endothelial cell loss was 13% (95% CI 2%–25%) and 23% (95% CI 17%–29%) in the group with air tamponade duration of below and above 2 hours, respectively (P = .126). At 3 months after surgery, it was 31% (95% CI 17%–42%) and 42% (95% CI 32%–52%) in the respective groups (P = .229).A postsurgical air tamponade of at least 2 hours with an IOP within the physiological range could help to reduce rebubbling rates.