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To investigate 1-year clinical outcome and complication rates following Descemet membrane endothelial keratoplasty (DMEK) with sulfur hexafluoride 20% (SF620%) anterior chamber tamponade compared with conventionally used 100% air for primary graft attachment during DMEK surgery.Records of 1112 consecutive DMEKs were reviewed retrospectively and grouped by anterior chamber tamponade used during DMEK surgery (SF620% vs 100% air). Outcome measures included intraocular pressure (IOP), best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD) and central corneal thickness (CCT) at 1, 3, 6 and 12 months after DMEK surgery. Complication rates were assessed, including intraoperative and postoperative complications, and graft detachment rate requiring rebubbling.A total of 854 cases were included in this study. In 105 cases (12.3%), DMEK was performed with SF620%, and in 749 cases (87.7%) 100% air was used for anterior chamber tamponade. Outcome results for IOP, BSCVA, ECD and CCT at all follow-up time points were comparable for both anterior chamber tamponade groups without statistical significant differences (p≥0.05), but graft detachment rate requiring rebubbling was significantly lower in the SF620% group (p<0.001).Whereas SF620% anterior chamber tamponade does not seem to negatively affect the clinical outcome of DMEK surgery within the first postoperative year, use of SF620% significantly reduces the rate of rebubblings.