Coronary arteritis rather than myocardial involvement is typically emphasized in Kawasaki disease (KD). Moreover, the criteria and the usual biological markers oversee the importance of cardiac-specific markers in diagnosing this disease. We sought to study the clinical usefulness of measuring B-type natriuretic peptide (BNP) and its N-terminal moiety (NT-proBNP) at the onset of KD. Our objective was to evaluate blood concentrations of BNP and NT-proBNP during the acute and subacute phases of KD. We conducted a prospective study comparing newly diagnosed KD patients to non-KD febrile controls. Blood specimens were collected at presentation, 6–12 h after intravenous immunoglobulin (IVIG) therapy, 1–2 weeks later, and 2–3 months later, or only upon reenrollment for controls. Forty-there KD and 19 control patients were enrolled consecutively. The mean age was 47.1 ± 34.3 and 62.2 ± 44.9 months, respectively (p = NS). Pre-IVIG NT-proBNP levels were significantly higher in KD patients than in controls (923.6 ± 1361.7 vs. 186.2 ± 198.0 ng/L; p < 0.001), with no statistical difference for BNP (141.9 ± 227.5 vs. 59.9 ± 72.4 ng/L; p = 0.112). In conclusion, our data indicate that NT-proBNP is a better marker of myocardial involvement in acute KD than BNP, particularly in cases with incomplete diagnostic criteria, and suggest that it may be a valid adjunctive diagnostic method to support the diagnosis of KD.