The objective of this study is to determine whether the data of blood profiles before and after therapy can be useful for predicting medium-giant coronary artery aneurysms (CAA) in patients with KD. In total, 1856 KD children from 2013 to 2022 were prospectively recruited. Serial blood samples on the day of initial IVIG infusion and 36-48 h thereafter were collected. The clinical and laboratory parameters were compared between the medium-giant CAA (n = 95) group and the non-CAA group (n = 1761). Multivariate analysis was performed to explore the independent risk factors for medium-giant CAA and the receiver operating characteristic (ROC) curve was used to evaluate and assess the prediction validities. Fever duration prior to initial IVIG infusion, IVIG resistance, cardiac enlargement, white blood cells prior to initial IVIG treatment, albumin levels, and the percentage of △neutrophils were independent risk factors for predicting medium-giant CAA. The predictive value of △neutrophil percentage (≤ 30.2%) demonstrates a relatively high sensitivity (0.84) and a moderate specificity (0.52) for predicting acute medium-giant CAA. The △neutrophil percentage before and 36-48 h after initial IVIG infusion might serve as a promising biomarker in the prediction of medium-giant CAA for KD patients.