Abstract Purpose To investigate changes in relative peripheral refraction (RPR) associated with myopia progression in children who wore single‐vision (SV) lenses for 2 years and switched to Defocus Incorporated Multiple Segments (DIMS) lenses in the third year versus children who wore DIMS lenses for 3 years. Methods In the first 2 years, children were allocated randomly to wear either DIMS or SV lenses. In the third year, children in the DIMS group continued to wear these lenses, while those in the SV group were switched to DIMS lenses (Control‐to‐DIMS group). Central and peripheral refraction and axial length were monitored every 6 months. Results Over 3 years, the DIMS group ( n = 65) showed good myopia control and maintained a relatively constant and symmetrical RPR profile without significant changes. In the first 2 years, children who wore SV lenses ( n = 55) showed asymmetrical RPR changes, with significant increases in hyperopic RPR at 20° nasal (N) (mean difference: 0.88 ± 1.06 D, p < 0.0001) and 30N (mean difference: 1.07 ± 1.09 D, p < 0.0001). The Control‐to‐DIMS group showed significant myopia retardation after wearing DIMS lenses in the third year. When compared with the RPR changes in the first 2 years, significant reductions in hyperopic RPR were observed at 20N (mean difference: −1.14 ± 1.93 D, p < 0.0001) and 30N (mean difference: −1.07 ± 1.17 D, p < 0.0001) in the third year. However, no significant difference between the RPR changes found in the nasal retina and temporal retina ( p > 0.05) was noted in the third year. Conclusion Symmetrical changes in RPR were found in children switching from SV to DIMS lenses, and a symmetrical pattern of RPR was noted in children who wore DIMS for 3 years. Myopia control using myopic defocus in the mid‐periphery influenced the RPR changes and retarded myopia progression by altering the eye's growth pattern.