PURPOSE: The purpose of this study was to assess whether omission of dextran from corneal organ culture medium alters the outcome of Descemet membrane endothelial keratoplasty. METHODS: Participation in this single-center, multisurgeon, prospective, randomized, comparative clinical trial was offered to patients scheduled for Descemet membrane endothelial keratoplasty between April 2020 and May 2022. Patients received grafts from corneas deswollen in organ culture medium-containing 6% dextran T-500 or from corneas that were not deswollen. Corrected distance visual acuity (CDVA), graft detachment, central corneal thickness (CCT), and corneal endothelial cell counts were measured at different time points up to 12 months postoperatively. RESULTS: Grafts stored with dextran were transplanted in 92 patients, and grafts stored without dextran were transplanted in 102 patients. Mean donor age and endothelial cell counts did not differ significantly between both groups. Mean (±SD) postmortem time in hours was 23.9 ± 11.8 in grafts that were deswollen and 28.2 ± 13.8 in grafts that were not deswollen ( P = 0.02). The groups did not show any significant difference at baseline regarding sex, CDVA, or CCT. In the group with dextran, patients had a mean age of 72.5 ± 9.9 years versus 69.5 ± 8.7 in the group without dextran ( P = 0.03). CDVA improved and CCT decreased significantly in both groups. No differences were detected between the groups regarding CDVA, CCT, endothelial cell counts, or rebubbling rates. CONCLUSIONS: This study did not detect any evidence that the omission of dextran from organ culture medium negatively affects the outcomes of Descemet membrane endothelial keratoplasty.