The diagnosis of acute Kawasaki disease (KD) is based on characteristic clinical signs and not on a specific diagnostic test. The authors performed a comprehensive evaluation of acute-phase reactants in KD to determine which of the acute-phase reactants would most accurately distinguish KD from other febrile illnesses. Blood was collected from 218 cases of febrile children with KD (64 cases); bacterial pneumonia (74 cases); hand, foot, and mouth disease (31 cases); and upper respiratory tract infection (49 cases) in acute-stage illness before any therapy. The demographics, body temperature, and laboratory markers including white blood cell count, red blood cell count, and levels of hemoglobin, platelets, C-reactive protein, haptoglobin, apolipoprotein A-I, and apolipoprotein B were evaluated. Using post hoc analysis, the platelet count (10(3)/μl) and haptoglobin/apolipoprotein A-I ratio were significantly higher for the KD patients (404.64 ± 161.68, P = 0.004; 4.74 ± 2.73, P < 0.001) than for the other groups including patients with pneumonia (272.76 ± 115.07, 2.03 ± 1.88); hand, foot, and mouth disease (274 ± 105.9, 2.24 ± 1.19); and upper respiratory tract infection (282.06 ± 107.72, 1.4 ± 0.98). The best cutoff value of the haptoglobin/apolipoprotein A-I ratio obtained from receiver operating characteristics (ROC) curves for KD was 2 (area under the ROC curve, 0.88; 95% confidence interval, 0.801-0.955), with a sensitivity of 89.7% and a specificity of 85.6% for detecting KD. Our data indicate that the serum haptoglobin/apolipoprotein A-I ratio could be a useful supplemental laboratory marker for the acute phase of KD.