Purpose:The aim of this study was to compare the long-term outcome of Descemet membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK).Methods:Records of consecutive DMEK surgeries performed between 2015 and 2016 at the Department of Ophthalmology, Cologne, Germany, were retrospectively reviewed from the prospective Cologne DMEK Database. Eyes with either PBK or FECD with a complete 3-year follow-up were enrolled. Main outcome parameters included central corneal thickness (CCT), peripheral corneal thickness (PCT), best spectacle-corrected visual acuity (BSCVA, logarithm of the Minimum Angle of Resolution), and endothelial cell count (ECC) before and after DMEK.Results:Four hundred two eyes from 402 patients were included (FECD n = 371, PBK n = 31). Preoperatively, CCT (FECD: 681.91 ± 146.78 μm; PBK: 932.25 ± 319.84 μm) and PCT (FECD: 732.26 ± 98.22 μm; PBK: 867.54 ± 88.72 μm) were significantly higher in the PBK group (P < 0.01). Three years after DMEK, CCT (FECD: 526.56 ± 27.94 μm; PBK 663.71 ± 132.36 μm) was significantly lower in both groups compared with the preoperative values (P < 0.01), whereas PCT showed no significant difference. PCT increased during the course in the PBK group from month 12 after DMEK (12 mo: 783.73 ± 127.73 μm; 24 mo: 837.50 ± 110.19 μm; 36 mo: 857.79 ± 140.76 μm). The increase in PCT correlated with an accelerated ECC loss starting 12 months after DMEK (P = 0.036). Before DMEK, BSCVA in FECD was significantly higher (P < 0.001) compared with that in PBK. After 3 years, BSCVA improved in FECD and PBK eyes without significant difference (P = 0.239).Conclusions:Visual acuity after DMEK in PBK and FECD seems to be comparable during the long-term follow-up. Peripheral and central corneal edema seems to recur faster in eyes with PBK than in those with FECD. Therefore, using a donor graft with higher ECC or possibly a larger graft could be a promising approach for PBK patients.