AIM: To explore the efficacy of the orthokeratology lens for anisometropic myopia progression. METHODS: A retrospective study was performed. Cycloplegic refraction and axial length (AL) were collected from 50 children (10.52±1.72y) who visited Peking University Third Hospital from July 2015 to August 2020. These children’s one eyes (Group A) received monocular orthokeratology lenses at first, after different durations (12.20±6.94mo), their contralateral eyes (Group B) developed myopia and receive orthokeratology as well. The data in 1-year of binocular period were recorded. AL growth rate (difference of follow-up and baseline per month) were compared between two groups by paired t test. Interocular differences of AL were compared by Wilcoxon test. RESULTS: During monocular period, the AL growth rate of the Group A (0.008±0.022 mm/mo) was significantly slower than that of the Group B (0.038±0.018 mm/mo; P<0.0001). However, during binocular period, the AL growth rate of the Group A (0.026±0.014 mm/mo) was significantly faster than that of the Group B (0.016±0.015 mm/mo; P<0.0001). The AL difference between both eyes was 0.6 (0.46) mm, then significantly decreased to 0.22 (0.39) mm when started binocular treatment (P<0.0001). However, it was significantly increased to 0.30 (0.32) mm after a year (P<0.0001), but still significantly lower than baseline (P<0.0001). CONCLUSION: The orthokeratology lens is efficient for control the AL elongation of monocular myopia eyes and reduce anisometropia. For the condition that the contralateral eyes develop myopia and receive orthokeratology lens later, there is no efficiency observed on control interocular difference of AL during binocular treatment.