Background/Objectives <p>To examine the two-to-three-year effectiveness and safety of accelerated corneal crosslinking (CXL) treatment performed by ophthalmic nurses for progressive keratoconus and to evaluate the potential prognostic factors for disease progression.</p> Methods <p>All consecutive eligible patients with progressive keratoconus who underwent nurse-led CXL between February 2019 and December 2021 at the Birmingham and Midland Eye Centre, UK, were included. A standardised accelerated, epithelium-off CXL protocol was employed, using 10 mW/cm² ultraviolet-A irradiation for 9 min (5.4 J/cm²). Relevant data, including demographics, corrected-distance-visual-acuity (CDVA), corneal tomographic findings, outcomes and adverse event, were analysed. Only patients that had completed at least a 2-year follow-up post-CXL were included.</p> Results <p>We included 97 patients (<i>n</i> = 97 eyes); mean age was 26.4±6.5 years and 52.6% were female. Most patients had mild (stage I) keratoconus (49.5%). From baseline to 24-month post-CXL (<i>n</i> = 97 eyes), there was a significant improvement in CDVA, (0.30 ± 0.22 logMAR vs. 0.20±0.18 logMAR; <i>p</i> &lt; 0.001) and Kmax (59.1±6.8 D vs. 58.1±6.4 D; <i>p</i> &lt; 0.001), with similar K1, K2 and thinnest corneal pachymetry (all <i>p</i> &gt; 0.05). There were three (3.1%) cases of clinically significant transient corneal haze noted at 1-week post-CXL. No significant adverse events such as corneal infection/melting were observed. At 36-month post-CXL (<i>n</i> = 31 eyes), the CDVA remained stable, with a significant improvement in Kmax (<i>p</i> &lt; 0.001) and K2 measurements (<i>p</i> = 0.038) from baseline.</p> Conclusions <p>This study highlights the efficacy, safety and feasibility of nurse-led CXL, serving as a valuable initiative in addressing the increased service demand for keratoconus management and preserving the vision of patients with keratoconus.</p>