This interventional case series looked at the influence of different intraoperative air tamponade times on graft adherence after descemet membrane endothelial keratoplasty (DMEK). A total of 117 eyes with Fuchs endothelial corneal dystrophy (FECD) that underwent DMEK were included. Patients were categorised into three groups according to intraoperative air (100% air) tamponade times of 60 minutes (group I; n=39), 45 minutes (group II; n=39), or 30 minutes (group III; n=39) before air-balanced salt solution (BSS) exchange leaving a 30% air bubble in phakic eyes and a 50% air bubble in pseudophakic eyes. Patients were instructed to remain supine from 48 to 72 hours after surgery. At one and six months postoperatively, graft adherence status (anterior segment OCT), endothelial cell density, central pachymetry, and postoperative complications were recorded. At one month, 19 of the 117 eyes (16.2%) showed a clinically significant detachment (>1/3 of the graft surface area and affecting visual axis): six eyes in group I (15.4%), five eyes in group II (12.8%), and eight eyes in group III (20.5%) (P=0.82). The overall rebubbling rate was 11%, with no difference among the groups (P=0.07). No association could be found between the presence of a major detachment and sex (host or donor), age (host or donor), lens status, donor diabetic status or storage time. Corneal thickness showed an overall decrease but no differences were observed between the groups. Although lower endothelial cell density could be expected due to toxic effect of air, no differences in one or six month postoperative ECD were observed among the groups. The study showed that the incidence of graft detachment after DMEK for FECD did not differ between the eyes that had a 60-, 45- or 30-minute intraoperative air tamponade. Reducing the intraoperative air tamponade time to 30 minutes may be considered for DMEK in eyes with uncomplicated FECD. The authors suggested that achieving a firm eye (around 20-25mmHg) during the full air tamponade and after having reduced the air bubble size before discharge is mandatory to have a good graft attachment.