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To describe the clinical outcome and histopathology of Descemet membrane endothelial keratoplasty (DMEK) performed for secondary graft failure after penetrating keratoplasty (PK).A total of 11 eyes from 10 patients who underwent DMEK for secondary PK graft failure at a tertiary referral center were included in this retrospective study. Best-corrected visual acuity, endothelial cell density, and central pachymetry were evaluated before and at regular time intervals up to 36 months after DMEK and complications were recorded; 1 post mortem cornea was available for light microscopy.At their last follow-up visit (on average, 16 months after DMEK), 7 of 11 transplanted corneas were clear. In the 7 eyes with clear grafts, 5 had a best-corrected visual acuity of ≥20/25 (≥0.8), central pachymetry averaged 535 (±70) μm, and endothelial cell density averaged 1045 (±500) cells/mm2. Of the 11 eyes, 4 required rebubbling in the early postoperative phase; 1 eye was left with a small (<1/3) detachment. Light microscopy of the pathology specimen showed complete attachment of the DMEK graft onto the preexisting PK posterior stroma, with interface scarring over DMEK graft folds and underneath the graft area that had initially been detached.DMEK may be a viable option to manage secondary PK graft failure with acceptable outcomes in many cases. Rebubbling for graft detachment may be anticipated, especially because of preexisting glaucoma conditions (severe decompensation, hypotony, and tubes from glaucoma-draining devices). Graft reattachment may occur through interface scarring.