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To evaluate 3-year outcomes of femtosecond laser-assisted Descemet membrane endothelial keratoplasty (F-DMEK) compared with manual Descemet membrane endothelial keratoplasty (M-DMEK) in patients with Fuchs endothelial corneal dystrophy (FECD).A retrospective, interventional study, including eyes with FECD and cataract that underwent either F-DMEK or M-DMEK combined with cataract extraction at either the Toronto Western Hospital or Kensington Eye Institute, and that had at least 18 months' follow-up was conducted. Exclusion criteria: complicated anterior segments, previous vitrectomy, previous keratoplasty, corneal opacity, or any other visually significant ocular comorbidity.Included were 16 eyes of 15 patients in the F-DMEK group (average follow-up 33.0 ± 9.0 months) and 45 eyes of 40 patients in the M-DMEK group (average follow-up 32.0 ± 7.0 months). There were no issues with the creation of femtosecond descemetorhexis (in the F-DMEK group)—all descemetorhexis cuts were complete. Best spectacle-corrected visual acuity improvement did not differ significantly between the groups at 1, 2, and 3 years (P = 0.849, P = 0.465 and P = 0.936, respectively). Rates of significant detachment in F-DMEK and M-DMEK were 1 of 16 eyes (6.25%) and 16 of 45 eyes (35.6%) (P = 0.027). Rebubbling rates were 1 of 16 eyes (6.25%) and 15 of 45 eyes (33.3%) (P = 0.047). Cell-loss rates following F-DMEK and M-DMEK were 26.8% and 36.5% at 1 year (P = 0.042), 30.5% and 42.3% at 2 years (P = 0.008), 37% and 47.5% at 3 years (P = 0.057), respectively. Graft failure rate was 0% in F-DMEK and 8.9% in M-DMEK (all were primary failures; P = 0.565).F-DMEK showed good efficacy with reduced detachment, rebubble, and cell-loss rates, compared with M-DMEK.