To evaluate the midterm outcomes of Descemet membrane endothelial keratoplasty (DMEK) up to 4-7 years postoperatively. Retrospective, consecutive interventional case series. A total of 250 consecutive eyes of 209 patients who underwent DMEK at our institute and had potentially at least 4 years of follow-up. Main outcome measures were best-corrected visual acuity (BCVA), endothelial cell density (ECD), central corneal thickness (CCT), graft survival rate, and postoperative complications. At 6months postoperatively, 73% of the eyes reached a BCVA of ≥20/25 (0.8) and 44% ≥20/20 (1.0), and remained stable up to 7 years (P= .7114). ECD dropped by 33.9% in the first 6months, and then declined by a yearly rate of 9.0%. CCT did not show a significant change after 6months up to 7 years (P= .8447). The cumulative graft survival rate at 4 and 7 years was 0.96 (95% confidence interval [0.93, 0.99]). Rebubbling procedures were performed in 4.4% of eyes, all within the first 6 postoperative months. Repeat transplantations were performed in 15.2% of cases to manage greater than one third graft detachment (11.6%), primary graft failure (1.6%), or secondary graft failure (2.0%), with the majority (79%) of repeat transplantations performed within the first year. After 6months, the main complications were allograft rejection (2.4%) and secondary graft failure (2.0%). The visual acuity level achieved at 6months after DMEK may remain stable up to at least 4-7 years; ECD shows a constant, slow decrease; and complications after the first 6months occur in <5% of cases.