PurposeTo investigate axial elongation (AE) and changes in relative peripheral refraction (RPR) in anisomyopic children undergoing orthokeratology (ortho‐k).MethodsBilateral anisomyopic children, 7–12 years of age, were treated with ortho‐k. Axial length (AL) and RPR, from 30° nasal (N30°) to 30° temporal (T30°), were measured at baseline and every 6 months over the study period. AE, changes in RPR and changes in the interocular AL difference were determined over time.ResultsTwenty‐six of the 33 subjects completed the 2‐year study. The AE of the higher myopic (HM) eyes (at least 1.50 D more myopia than the other eye) (0.26 ± 0.29 mm) was significantly smaller than for the less myopic (LM) eyes (0.50 ± 0.27 mm; p = 0.003), leading to a reduction in the interocular difference in AL (p = 0.001). Baseline RPR measurements in the HM eyes were relatively more hyperopic at T30°, N20° and N30° (p ≤ 0.02) and greater myopic shifts were observed at T20° (p < 0.001), T30° (p < 0.001), N20° (p = 0.02) and N30° (p = 0.01) after lens wear. After 2 years of ortho‐k lens wear, temporal–nasal asymmetry increased significantly, being more myopic at the temporal locations in both eyes (p < 0.001), while AE was associated with the change in RPR at N20° (β = 0.134, p = 0.01). The interocular difference in AE was also positively associated with the interocular difference in RPR change at N30° (β = 0.111, p = 0.02).ConclusionsOrtho‐k slowed AE in bilateral anisomyopia, with slower growth in the HM eyes leading to a reduction in interocular AL differences. After ortho‐k, RPR changed from hyperopia to myopia, with greater changes induced in the HM eyes, and slower AE was associated with a more myopic shift in RPR, especially in the nasal field of both eyes.