Objective To present the study design and the baseline data of a prospective cohort study investigating the safety, refractive correction and effectiveness of myopia control in subjects fitted with orthokeratology (ortho-k) lenses of different compression factors.Methods and analysis This study is a 2-year longitudinal, double-masked, partially randomised study. Myopic children aged between 6 and 10 years are recruited and they may choose to participate in either the ortho-k or spectacle-wearing group. Subjects in the ortho-k group are randomly assigned to wear ortho-k lenses of either conventional compression factor (CCF, 0.75 D) or increased compression factor (ICF, 1.75 D). For the ortho-k subjects, the time and between-group effects within the first month of lens wear were analysed.Results Sixty-nine ortho-k subjects (CCF: 34; ICF: 35) and 30 control subjects were recruited. There were no significant differences in baseline demographic data among the three groups of subjects (pgt;0.19). At the 1-month visit, the first fit success rates were 9700k group, respectively. A higher percentage of ICF subjects could achieve full correction (CCF: 88.2 ICF: 94.3. The change in axial length was significantly higher in the ICF group (CCF, 0.003 mm; ICF, -0.031 mm) (plt;0.05). No significant between-group differences in daytime vision or in the coverage and depth of corneal staining between the two ortho-k groups (pgt;0.05) were observed at any visit.Conclusion ICF did not compromise the corneal integrity and the lens centration within the first month of lens wear. The preliminary performance of ortho-k lenses with ICF of 1.00D shows that it was safe to be used in the longer term for the investigation of myopia control.Trial registration number NCT02643342.