To investigate the relationship between the risk factors associated with intravenous immunoglobulin (IVIG) non-response and the incidence of coronary artery lesions (CAL) in patients with Kawasaki disease (KD). A retrospective study was performed on clinical records of 1953 KD patients who were admitted to hospitals in Shanghai, China, between 1998 and 2007. Related clinical and laboratory findings were studied using univariate and multivariate statistical analyses. Of the 1953 KD patients, 133 (6.8 %) were unresponsive to IVIG therapy, and 356 (18.6 %) developed CAL. The incidence of CAL in the non-responsive IVIG group was significantly different from that in the responsive IVIG group (31.3 vs. 17.6 %). The incidence of IVIG non-response was significantly lower in the patients who received sufficient doses of IVIG than in the patients who received insufficient doses (5.2 vs. 18.1 %). A logistic regression analysis of 1295 patients who received sufficient IVIG doses indicated that cervical lymph node enlargement, CAL, erythrocyte sedimentation rate (ESR) ≥75 mm/h, and platelet count (PLT) ≥530 × 10⁹/L were independent risk factors of IVIG non-response. IVIG non-responders are prone to develop CAL. Initiation of therapy with sufficient IVIG doses at the early stage of the disease is crucial for preventing IVIG non-response. Lymph node enlargement, ESR ≥75 mm/h, and PLT count ≥530 × 10⁹/L are independent risk factors for predicting non-response to sufficient IVIG doses. For patients with the tendency of being unresponsive to IVIG therapy, treatment using sufficient IVIG doses combined with hormones or immunosuppressive agents should be considered to reduce the incidence of IVIG non-response and CAL.