OBJECTIVE: Intravenous immunoglobulin (IVIG) resistance is associated with coronary artery abnormalities in Kawasaki disease (KD) and requires additional therapy. The purpose of this study was to determine independent risk factors for IVIG resistance, investigate the response to IVIG treatment at different time points and determine whether the time option of IVIG treatment altered IVIG resistance. METHODS: The clinical data of 6264 KD patients in southwest China were analyzed retrospectively. According to the response to IVIG treatment, the patients were divided into IVIG response group and IVIG resistance group. Multiple logistic regression model was used to identify independent risk factors for IVIG resistance, and trend chi-square test was used to examine the effect of IVIG timing on IVIG resistance. RESULTS: Multivariate analysis showed that IVIG time, WBC, PLT, HB, ALT and Na were independently associated with IVIG resistance, and IVIG time was a key variable for IVIG resistance. In addition, these data suggested that the rate of IVIG resistance was the lowest when treated with IVIG on the seventh and eighth day of initial fever. CONCLUSION: IVIG timing is a key factor in IVIG resistance. Our data suggest a lower resistance rate when IVIG is administered on the seventh and eighth day of initial fever. However, the clinical implications of delaying treatment are uncertain, and early IVIG administration remains essential to prevent cardiovascular complications. Further research is needed to validate these findings and to guide clinical practice.