AIM: To explore the effect of eccentricity of overnight orthokeratology (OK) lenses on 2-year eye axial growth and visual quality. METHODS: Based on the degree of eccentricity of OK lenses, patients were divided into three groups: a low degree of eccentricity group (degree of eccentricity ≤0.5 mm), a group of moderate eccentricity (eccentric degree >0.5-1.0 mm) and a group with a high degree of eccentricity (eccentric degree >1-1.5 mm). The degree of eccentricity of the OK lens, spherical equivalent (SE), the uncorrected visual acuity (UCVA) after wearing OK lenses, axial length (AL) before and after wearing OK lenses, total higher-order aberrations (HOA), comas, and spherical aberrations (SA) for 3 mm pupils were analyzed. The difference among the three groups for all parameters was compared using the Kruskal-Wallis H Rank-Sum test. RESULTS: The study retrospectively analyzed 75 cases (139 eyes). In the low eccentricity group (53 eyes), the mean age was 11.4±2.4y, SE was -3.24±1.48 D, and AL was 24.85±1.01 mm. In the moderate eccentricity group (53 eyes), the mean age was 11.4±2.2y, SE was -3.22±1.29 D, and AL was 25.15±0.92 mm. In the high eccentricity group (31 eyes), the mean age was 11.5±1.9y, SE was -3.54±1.43 D, and AL was 24.95±0.84mm. After two years, there was no significant difference in the changes of the axis among the three groups (P=0.089). The HOA, SA, and coma in the high eccentric group were significantly higher than in the middle eccentric group (P<0.05). The HOA, SA, and coma in the high eccentric group were also significantly higher than those in the low eccentric group (P<0.05). CONCLUSION: For OK lenses, it is unnecessary to strictly require the absolute centralization of the lens position. An unnecessary change of the lenses may delay the eye-axis control. However, the balance between axial control and visual quality should be assessed.