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PURPOSE To present 24-month results from the transepithelial photorefractive keratectomy (PRK)-corneal crosslinking (CXL) trial using simultaneous accelerated CXL and a new tissue-saving ocular wavefront-guided transepithelial PRK algorithm aiming to reverse visual loss in early-stage keratoconus without compromise to stabilization of disease progression. SETTING Moorfields Eye Hospital, London, United Kingdom. DESIGN Prospective case series. METHOD Patients with progressive grades I to III keratoconus and logarithm of the minimum angle of resolution (logMAR) corrected distance vision acuity (CDVA) worse than 0.00 (20/20) were included. Consecutive matched historical controls treated only with accelerated CXL were the control group. The main outcome measure was change in logMAR CDVA. RESULTS The study group comprised 47 eyes of 47 patients (mean age 24.6 years ± 3.8 [SD]). The CDVA improved from 0.28 ± 0.21 logMAR (20/60) preoperatively to 0.15 ± 0.14 logMAR (20/30) 24 months after transepithelial PRK-CXL (P < .001). Twelve eyes gained and 1 eye lost 2 lines or more of CDVA. The mean stromal ablation depth at the cone apex was 35 ± 15 μm. Significant reductions in the maximum keratometry (K) reading and coma were evident in topographic comparison maps. The controls (n = 47) had no significant changes in CDVA, higher-order aberrations, or K values. The mean K values in both groups were stable from 6 months after treatment. CONCLUSION Ocular wavefront-guided transepithelial PRK-CXL resulted in significant gains in CDVA without compromising CXL efficacy over a 24-month follow-up.