Purpose: To evaluate the clinical outcome and complications of Descemet membrane endothelial keratoplasty (DMEK), using Descemet-stripping endothelial keratoplasty (DSEK) as a back-up procedure, in the management of Fuchs endothelial dystrophy. Design: Non-randomised prospective clinical study. Methods: The first fifty consecutive eyes that underwent DMEK, that is, transplantation of an isolated donor Descemet membrane carrying its endothelium, for Fuchs endothelial dystrophy were evaluated. In all eyes, the best-corrected visual acuity (BCVA) as well as the endothelial cell density (ECD) was measured before and at 6 months after surgery, as clinical outcome parameters. Results: Ten patients required a secondary DSEK for failed DMEK. In the remaining 40 DMEK eyes, 95% had a BCVA of X20/40 (X0.5) and 75% X20/25 (X0.8) at 6 months after surgery. ECD averaged 2618 ( ± 201) cells/mm 2 before, and 1876 ( ± 522) cells/mm 2 at 6 months after surgery (n ¼ 35). When the outcomes of DMEK and secondary DSEK procedures were combined, 94% reached a BCVA of X20/40 (X0.5) and 66% X20/25 (X0.8) (n ¼ 47), and ECD averaged 2623 ( ± 193) cells/mm 2 before, and 1815 ( ± 578) cells/mm 2 at 6 months after surgery (n ¼ 43). Conclusion: With DSEK as a back-up procedure, DMEK may provide relatively quick and complete visual rehabilitation in a majority of patients operated on for Fuchs endothelial dystrophy. Endothelial cell survival may be similar to earlier types of (lamellar) keratoplasty. Early graft detachment was the main complication in this first series of DMEK surgeries for Fuchs endothelial dystrophy.