We aimed to investigate the changes in higher-order aberrations (HOAs) after wearing orthokeratology (OK) lenses in myopic patients. The study included 15 eyes from ten myopic patients, whose refractive error was myopia less than −4.5 diopters (D) and astigmatism less than 1.5 D. Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) were measured, and Zywave® aberrometry was performed at baseline and 1, 3, and 6 months following OK lens wear. The mean age was 11.5 years (range: 9–15 years). There was a significant improvement in UCVA (p ≤ 0.001) and a decrease in the spherical equivalent measured with auto-refraction at 6 months (p ≤ 0.001). Total HOAs significantly increased after OK lens wear (p ≤ 0.001), with spherical aberration increasing approximately 3.9-fold (p = 0.05). Spherical aberration demonstrated statistically significant positive correlations with the change in spherical equivalent at 3 and 6 months (p = 0.007 and 0.003, respectively). After wearing properly prescribed OK lens, all subjects had significantly improved UCVA and decreased myopic spherical equivalent, with increased total HOAs and positive spherical aberration at 1 month, and the changes were maintained at 6 months. Serially checked spherical aberration could evaluate the anti-myopia effect of the orthokeratology lens in children.