Purpose: To determine the influence of compression factor upon changes in axial length and choroidal thickness during and following orthokeratology treatment. Methods: Orthokeratology lenses of different compression factors (one eye with 0.75 D and the fellow eye with 1.75 D) were randomly assigned to 28 subjects (median [range] age: 9.3 [7.8–11.0] years). Ocular biometrics were measured weekly for 1 month of lens wear and after lens cessation until the refraction stabilized (mean duration: 2.8 ± 0.4 weeks). Changes between eyes, and the associations between axial shortening and choroidal thickening with other ocular biometrics were analyzed. Results: There were no significant between-eye differences in the changes of ocular biometrics (all P > 0.05). After adjusting for paired-eye data, axial length initially decreased by 26 ± 41 µm (P = 0.03) at week 1, then gradually returned to its original length. An approximate antiphase relationship of choroidal thickness (mean change: 9 ± 12 µm, P < 0.001) with axial length was observed. A significant rebound in axial length, but not choroidal thickness, occurred during the cessation period. Central corneal thinning and choroidal thickening accounted for 70% of initial axial shortening. Conclusions: Increasing the compression factor by 1.00 D did not affect changes in ocular biometrics in short-term orthokeratology. Significant axial shortening and choroidal thickening were observed during early treatment period. Axial shortening could not be entirely explained by central corneal thinning and choroidal thickening, which warrants further investigation. Translational Relevance: Initial axial shortening in orthokeratology is transient and therefore axial length remains useful for long-term monitoring of axial elongation in children.