To describe the clinical outcome and complications of repeat Descemet membrane endothelial keratoplasty (re-DMEK). Retrospective case series study at a tertiary referral center. From a series of 550 consecutive DMEK surgeries with ≥ 6 months follow-up, 17 eyes underwent re-DMEK for graft detachment after initial DMEK (n = 14) and/or endothelial graft failure (n = 3). The outcomes were compared with an age-matched control group of uncomplicated primary DMEK surgeries. The re-DMEK eyes were evaluated for best-corrected visual acuity (BCVA), densitometry, endothelial cell density (ECD), pachymetry, and intraoperative and postoperative complications. Feasibility and clinical outcome of re-DMEK. In all eyes, re-DMEK was uneventful. At 12 months, 12 of 14 eyes (86%) achieved a BCVA of ≥ 20/40 (≥ 0.5); 8 of 14 eyes (57%) achieved ≥ 20/25 (≥ 0.8), 3 of 14 eyes (21%) achieved ≥ 20/20 (≥ 1.0), and 1 eye (7%) achieved 20/17 (1.2); 5 eyes were fitted with a contact lens. Average donor ECD decreased from 2580 ± 173 cells/mm(2) before to 1390 ± 466 cells/mm(2) at 6 months after surgery, and pachymetry from 703 ± 126 μm to 515 ± 39 μm, respectively. No difference in densitometry could be detected between re-DMEK and control eyes (P = 0.99). Complications after re-DMEK included primary graft failure (n = 1), secondary graft failure (n = 2), graft detachment requiring rebubbling (n = 1), secondary glaucoma (n = 2), cataract (n = 1), and corneal ulcer (n = 1). One eye received tertiary DMEK. In the management of persistent graft detachment and graft failure after primary DMEK, re-DMEK proved a feasible procedure. Acceptable BCVA may be achieved, albeit lower than after DMEK in virgin eyes, and some cases may benefit from contact lens fitting. Complications after re-DMEK may be better anticipated than after primary DMEK because graft detachment and graft failure tended to recur, suggesting that intrinsic properties of the host eye play a role in graft adherence and graft failure.