PurposeTo evaluate the safety and efficacy of prophylactic Ripasudil in maintaining corneal endothelial function and preventing corneal failure in patients with late-stage Fuchs corneal dystrophy (FCD) undergoing femtolaser-assisted cataract surgery.Major findingsThis prospective, randomized, open-label, controlled interventional study included 41 eyes from 27 patients, 27 eyes treated with Ripasudil and 14 with hyaluronic acid as a control. Treatment was administered from 1 month before cataract surgery through 2 months postoperatively. Primary outcomes included best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell density and morphology, assessed at baseline, 3 months, and 9 months after surgery. Statistical analysis was performed using the unpaired t-test with Welch's correction and the Wilcoxon matched-pairs test, with a significance threshold of p < 0.05. The Ripasudil group showed a significant improvement in BCVA, from0.3 ± 0.3 to 0.2 ± 0.2 LogMAR (p = 0.01), along with stable CCT (556.3 ± 76.4 μm at baseline vs. 563.3 ± 72.2 μm at post-operative month 3, p = 0.39). In contrast, the control group demonstrated no significant improvement in BCVA (p = 0.13) and a significant increase in CCT (from 591.9 ± 59.3 μm to 658.4 ± 74.6 μm, p < 0.01). Endothelial cell density, polymegathism, and pleomorphism remained stable in both groups. At 9 months, Ripasudil-treated eyes continued to show stability in both BCVA and CCT, with no adverse events reported.ConclusionRipasudil demonstrated a protective effect on the corneal endothelium during cataract surgery in late-stage FCD patients, with better visual outcomes and reduced postoperative corneal edema.