ABSTRACT: Background: The prediction of intravenous immunoglobulin (IVIG) resistance and cardiovascular complications are critically clinical issues in Kawasaki disease (KD). This prospective study firstly aimed to determine the predictive ability of the systemic immune inflammation index (SII) for IVIG resistance and cardiovascular complications and compare the prognostic accuracy of SII with that of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). Methods: Patients with KD were divided into different groups according to the presence of IVIG resistance or cardiovascular complications (coronary artery lesions, valve regurgitation, myocarditis, pericardial effusion, and Kawasaki disease shock syndrome [KDSS]). The clinical and laboratory parameters were compared. Further analysis stratified by platelet level was performed. Multivariate logistic regression analysis was used to identify predictors for IVIG resistance and cardiovascular complications. The receiver operating characteristic (ROC) curve was applied to assess and compare the ability of SII, NLR, and PLR for predicting IVIG resistance and cardiovascular complications. Results: SII was significantly higher in KD patients with IVIG-resistance, myocarditis, valve regurgitation, and KDSS. It was identified as an independent risk factor for IVIG resistance, myocarditis, and valve regurgitation. For KD patients with thrombocytopenia, there were no significant differences in SII between KD patients with IVIG resistance/cardiovascular complications and those without. The best cutoff values of SII for IVIG resistance, myocarditis, valve regurgitation, and KDSS prediction in the whole cohort were 1331.4 × 109, 1368.6 × 109, 1002.4 × 109, and 1485.4 × 109, with a corresponding sensitivity of 0.525, 0.614, 0.754, and 0.670, a specificity of 0.711, 0.723, 0.584, and 0.730, respectively. The predictive value of SII for both IVIG resistance and cardiovascular complications were not superior to that of NLR. Conclusion: Although the parameter of SII may predict IVIG resistance, myocarditis, valve regurgitation, and KDSS in KD as a single parameter, its predictive ability was not good enough and not superior to NLR. SII might not be applicable in patients with KD having thrombocytopenia.