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Purpose To investigate the effect of overnight orthokeratology (OK) contact lens wear on axial length growth in East Asian children with progressive myopia. Design A prospective, randomized, contralateral-eye crossover study conducted over a 1-year period. Participants We enrolled 26 myopic children (age range, 10.8–17.0 years) of East Asian ethnicity. Methods Subjects were fitted with overnight OK in 1 eye, chosen at random, and conventional rigid gas-permeable (GP) lenses for daytime wear in the contralateral eye. Lenses were worn for 6 months. After a 2-week recovery period without lens wear, lens–eye combinations were reversed and lens wear was continued for a further 6 months, followed by another 2-week recovery period without lens wear. Axial eye length was monitored at baseline and every 3 months using an IOLMaster biometer. Corneal topography (Medmont E300) and objective refraction (Shin-Nippon NVision-K 5001 autorefractor) were also measured to confirm that OK lens wear was efficacious in correcting myopia. Main Outcome Measurements Axial length elongation and myopia progression with OK were compared with conventional daytime rigid contact lens wear. Results After 6 months of lens wear, axial length had increased by 0.04±0.06 mm (mean ± standard deviation) in the GP eye ( P = 0.011) but showed no change (−0.02±0.05 mm) in the OK eye ( P = 0.888). During the second 6-month phase of lens wear, in the OK eye there was no change from baseline in axial length at 12 months (−0.04±0.08 mm; P = 0.218). However, in the GP eye, the 12-month increase in axial length was significant (0.09±0.09 mm; P < 0.001). The GP lens-wearing eye showed progressive axial length growth throughout the study. Conclusions These results provide evidence that, at least in the initial months of lens wear, overnight OK inhibits axial eye growth and myopia progression compared with conventional GP lenses. Apparent shortening of axial length early in OK lens wear may reflect the contribution of OK-induced central corneal thinning, combined with choroidal thickening or recovery due to a reduction or neutralization of the myopiogenic stimulus to eye growth in these myopic children.