Purpose: This study analyzed real-world practice patterns, graft survival, and outcomes of Descemet membrane endothelial keratoplasty (DMEK) in the Netherlands. Design: Population-based interventional clinical study. Methods: In this prospective registry study, all consecutive primary DMEK procedures registered in the Netherlands Organ Transplant Registry were identified. Short-term graft survival and outcomes of primary transplants for Fuchs' endothelial dystrophy (FED) were analyzed using Kaplan-Meier survival curves with log-rank test and Cox regression. Linear mixed model analyses were used for best spectacle-corrected visual acuity (BSCVA), spherical equivalent, hyperopic shift, and endothelial cell density. Results: 752 DMEKs were identified between 2011 and 2018. In 90% of cases, the indication for DMEK was FED. Graft survival measured 87% at 3 months, 85% at 6 months, 85% at 1 year, and 78% at 2 years. DMEK procedures after 2015 showed better survival compared to previous years (Hazard ratio = 0.4; P < .001). Baseline BSCVA in primary transplants with FED measured on average 0.45 logarithm of the minimum angle of resolution (logMAR) (95% confidence interval [CI], 0.41-0.49), and significantly improved (overall P < .001) to 0.17 logMAR (95% CI, 0.14-0.21) at 3 months, 0.15 logMAR (95% CI, 0.11-0.18) at 6 months, 0.12 logMAR (95% CI, 0.08-0.16) at 1 year, and 0.08 (95% CI, 0.05-0.12) at 2 years. At 3 months, a hyperopic shift of +0.36 diopters (P < .001) was observed and endothelial cell loss measured 33%. Conclusion: Our findings provide real-world support that DMEK is an effective treatment for FED with respect to vision restoration, inducing a small hyperopic shift with an acceptable endothelial cell loss. Graft survival improved over time, suggesting a learning curve on a national level.