Purpose: To compare changes in relative peripheral refraction (RPR) associated with myopia progression in myopic children wearing Defocus Incorporated Multiple Segments (DIMS) lenses and single vision (SV) spectacle lenses over 2 years. Methods: A 2-year double-blind, randomized controlled trial was conducted on 183 myopic children. Subjects were allocated to either wearing DIMS (n = 93) or SV spectacle lenses (n = 90). Peripheral refraction at 10°, 20°, and 30° of the nasal (10N, 20N, 30N) and temporal (10T, 20T, 30T) retinal eccentricities, central refraction, and axial length after cycloplegia were monitored every 6 months. Results: DIMS group showed symmetrical peripheral myopic shifts between the nasal and temporal retina (comparing myopic shifts between the nasal and temporal retina, the difference between the corresponding eccentricities were nonclinically significance). SV group showed asymmetrical peripheral myopic shifts between the nasal and temporal retina, with more myopic shifts (all P ≤ 0.001) at 10T (-0.32 ± 0.62 diopters [D]), at 20T (-0.69 ± 0.95 D), and 30T (-0.85 ± 1.52 D). No significant changes in RPR spherical equivalent (M) were noted in the DIMS group, whereas significant increases (all P < 0.0001) in hyperopic RPR M were observed at 10N (0.27 ± 0.45 D), 20N (0.75 ± 0.72 D), and 30N (0.98 ± 0.76 D) in the SV group. Conclusions: Wearing DIMS lenses resulted in a significantly different peripheral refraction profile and RPR changes, as well as significant myopia control effects when compared with SV lenses. Myopia control adopting myopic defocus in the midperiphery influenced peripheral refraction and slowed central myopia progression, most likely through alteration of overall retinal shape.