Objective To analyze the relevant factors in decentration of the optical zone after overnight orthokeratology lens fitting. Methods This was a retrospective clinical study. One hundred and ten myopes (213 eyes, age range, 6.5～17.0 years) were fitted with overnight orthokeratology lenses. Patients were divided among 3 groups based on age: 6.5-10.0 years, group A; 11.0-13.0 years, group B; and 14.0-17.0 years, group C. Patients were divided into 2 groups based on their initial spherical diopter ＜-3.00 D group and -3.00- -6.00 D group. Patients were divided into 3 groups based on initial astigmatism: ＜0.50 D astigmatism group, 0.50-1.00 D astigmatism group, and ≥1.00 D astigmatism group. Based on the distance of decentration at 3 months after orthokeratology, patients were divided into 3 groups: ＜0.5 mm decentration group, 0.5-1.0 mm decentration group, and ≥1.0 mm decentration group. Corneal topography was measured before and 3 months after orthokeratology. The decentration (distance and angle) of the optical zone center after orthokeratology was calculated relative to the pupil center. Data were collected on the relevant factors affecting decentration after orthokeratology and the initial age, initial sperical diopter, initial astigmatism and initial corneal parameter. The data were analyzed with a t test, ANOVA test and Pearson correlation test. Results The mean distance for decentration 3 months after orthokeratology was 0.53±0.33 mm. The decentration was mainly located in the inferior temporal quadrant. After 3 months, a decentration distance of less than 0.5 mm was observed in 111 eyes (52.1%), 0.5-1.0 mm in 81 eyes (38.0%) and more than 1.0 mm in 21 eyes (9.9%). There was no statistically significant difference in the decentration distance between the three age groups. Patients with a higher initial sperical diopter (t=1.76, P＜0.05) and astigmatism (F=9.254, P＜0.05) showed a greater decentration distance. The initial corneal keratometry value evaluated with the topographic map showed that the nasal side of the cornea was flatter than the temporal side. The initial corneal keratometry value was greater in patients with severe decentration (P＜0.05). The correlation analysis showed that there was no significant correlation between decentration and the corneal parameter, but there was a positive correlation between decentration and initial spherical refractive error or initial astigmatism (r=0.354, 0.127, P<0.05). Conclusion Optical zone decentration can be seen due to the overnight orthokeratology process. The occurrence of decentration was associated with the initial refractive state and was affected by the natural physiological state of the cornea.