AIM: To evaluate related factors with the change of spherical equivalents (ΔSE) and determine the suitable predictor of clinically significant ΔSE (≥0.50 D) with cyclopentolate hydrochloride on Chinese children. METHODS: A total of 145 right eyes of 145 children aged 4 to 15y were enrolled. Intraocular pressure, axial length and lag of accommodation (LOA) were assessed before cycloplegia induced by 3 drops of 1% cyclopentolate at 5-minute intervals. SE was measured before and 1h after the first drop of cyclopentolate. ΔSE was compared between different gender groups and among refractive groups. Multivariate linear regression analysis was performed to find related factors with ΔSE. ROC analysis was used to figure out the suitable predictor of clinically significant ΔSE. RESULTS: For the total 145 eyes, the mean SE reached up to -0.70±1.86 D from -1.30±1.62 D, with the mean ΔSE of 0.60±0.55 D. The mean ΔSE were 0.63±0.55 D and 0.57±0.56 D respectively in the male and female group (P=0.40). The mean ΔSE was significantly different among different refractive groups (P<0.0001), with the ΔSE of hyperopia group (1.12±0.64 D) larger than that of the emmetropia (0.56±0.43 D, P=0.001) and myopia group (0.32±0.28 D, P<0.0001). The ΔSE was correlated with LOA (B=-0.54, P<0.0001), cycloplegic SE (B=0.10, P<0.0001) and age (B=-0.04, P=0.015). ROC curve indicated that LOA predicted clinically significant ΔSE by 82% [area under the curve (AUC)=0.82] alone, while the value was slightly improved to 85% (AUC=0.85) in combination with axial length and 86% (AUC=0.86) in association with axial length as well as age. CONCLUSION: After cycloplegia with cyclopentolate, the ΔSE decreases with larger LOA, longer axial length and older age. Specifically, LOA plays a more vital role in predicting clinically significant ΔSE.