AIM: To present the 1-year results of a prospective cohort study investigating the efficacy, potential mechanism, and safety of orthokeratology (ortho-k) with different back optic zone diameters (BOZD) for myopia control in children. METHODS: This randomized clinical study was performed between Dec. 2020 and Dec. 2021. Participants were randomly assigned to three groups wearing ortho-k: 5 mm BOZD (5-MM group), 5.5 mm BOZD (5.5-MM group), and 6 mm BOZD (6-MM group). The 1-year data were recorded, including axial length, relative peripheral refraction (RPR, measured by multispectral refractive topography, MRT), and visual quality. The contrast sensitivity (CS) was evaluated by CSV-1000 instrument with spatial frequencies of 3, 6, 12, and 18 cycles/degree (c/d); the corneal higher-order aberrations (HOAs) were measured by iTrace aberration analyzer. The one-way ANOVA was performed to assess the differences between the three groups. The correlation between the change in AL and RPR was calculated by Pearson’s correlation coefficient. RESULTS: The 1-year results of 20, 21, and 21 subjects in the 5-MM, 5.5-MM, and 6-MM groups, respectively, were presented. There were no statistical differences in baseline age, sex, or ocular parameters between the three groups (all P>0.05). At the 1-year visit, the 5-MM group had lower axial elongation than the 6-MM group (0.07±0.09 vs 0.18±0.11 mm, P=0.001). The 5-MM group had more myopic total RPR (TRPR, P=0.014), with RPR in the 15°–30° (RPR 15–30, P=0.015), 30°–45° (RPR 30–45, P=0.011), temporal (RPR-T, P=0.008), and nasal area (RPR-N, P<0.001) than the 6-MM group. RPR 15–30 in the 5.5-MM group was more myopic than that in the 6-MM group (P=0.002), and RPR-N in the 5-MM group was more myopic than that in the 5.5-MM group (P<0.001). There were positive correlations between the axial elongation and the change in TRPR (r=0.756, P<0.001), RPR 15–30 (r=0.364, P=0.004), RPR 30–45 (r=0.306, P=0.016), and RPR-N (r=0.253, P=0.047). The CS decreased at 3 c/d (P<0.001), and the corneal HOAs increased in the 5-MM group (P=0.030). CONCLUSION: Ortho-k with 5 mm BOZD can control myopia progression more effectively. The mechanism may be associated with greater myopic shifts in RPR.