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To evaluate whether donor and/or recipient diabetes status affects the outcomes of Descemet membrane endothelial keratoplasty (DMEK).A consecutive, single-center DMEK case series was reviewed. The outcome measures were success of surgeon tissue preparation, air reinjection rate, Kaplan–Meier 4-year graft replacement/failure rate for any reason, and endothelial cell loss.The donor had a history of diabetes in 504 of 1791 cases (28%) and the recipient in 14%. For donors without and with diabetes, the preparation success rate was 99% versus 95% (P < 0.0001), the air reinjection rate was 16% versus 18% (P = 0.19), and the 4-year graft replacement/failure rate was 7% versus 9%, respectively (P = 0.15). Endothelial cell loss was not associated with donor diabetes (P = 0.76). For recipients without and with diabetes, the 4-year graft replacement/failure rate was 7% versus 9% (P = 0.68), and median endothelial cell loss increased from 27% versus 29% at 1 month to 42% versus 48% at 4 years, respectively (P = 0.02). Recipient use of insulin therapy was associated with poorer graft attachment and a higher air reinjection rate (P = 0.0023).Although donor diabetes was associated with a 5-fold increased risk of tissue preparation failure, it was not significantly associated with air reinjection, graft survival, or endothelial cell loss. This provides reassurance that tissue prepared successfully from donors with diabetes is safe to use for DMEK. Recipient diabetes was associated with increased endothelial cell loss; the potential effect on longer-term graft survival merits further study.