Descemetorhexis without endothelial keratoplasty (DWEK) is an innovative corneal intervention and potentially effective against Fuchs endothelial corneal dystrophy (FECD). We aimed to conduct a systematic review and meta-analysis on the outcomes of DWEK, associated or not with phacoemulsification (PKE) and rho-kinase inhibitor (RHOKI) in FECD. PubMed, Cochrane Library, Embase, ClinicalTrials.gov , and Science Direct were searched for studies until November 29, 2020. We performed random-effects meta-analyses and meta-regressions, stratified by the type of intervention and descemetorhexis size (PROSPERO CRD42020167566). We included 11 articles (mainly case series, both prospective and retrospective), representing 127 eyes of 118 patients. DWEK globally improved visual acuity (effect size = -1.11, 95% confidence interval, -1.70 to -0.52, P < 0.001) and pachymetry (-1.25, -1.92 to -0.57, P < 0.001), without significant effects on endothelial cell count (-0.59, -2.00 to 0.83, P = 0.419). The 3 types of interventions (ie, DWEK ± RHOKI, DWEK ± PKE, and DWEK ± PKE ± RHOKI) improved visual acuity and pachymetry in FECD. A descemetorhexis size ≤4 mm improved visual acuity (-0.72, -1.29 to -0.14, P < 0.001) and pachymetry (-0.68, -0.98 to -0.38, P < 0.001), whereas >4 mm did not. Overall, DWEK failure (ie, the prevalence of EK after DWEK) was 17% (7%-27%, P < 0.001), with 4% (0%-8%, P = 0.08) for a descemetorhexis size ≤4 mm. Despite the lack of comparative studies, DWEK seemed to improve visual acuity and pachymetry in early stages of FECD. A descemetorhexis size ≤4 mm was associated with the best visual outcomes and pachymetry. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.