Objectives: B-type natriuretic peptide, a cardiac hormone with diuretic, natriuretic, and vasoactive properties, is used in the diagnosis, risk stratification, and management of adult cardiac patients. However, no study has yet determined the prognostic value of B-type natriuretic peptide after surgical intervention for congenital heart disease. The objectives of this study were (1) to determine alterations in B-type natriuretic peptide levels after repair of congenital heart disease with cardiopulmonary bypass and (2) to investigate potential associations between B-type natriuretic peptide levels and outcomes in this patient population. Methods: Fifty-one infants and children undergoing repair of congenital heart disease were studied. B-type natriuretic peptide levels were measured before and after surgical intervention, and the ability of the postoperative 12-hour B-type natriuretic peptide level to predict postoperative outcomes was evaluated. Results: B-type natriuretic peptide levels increased after separation from cardiopulmonary bypass, with an 8-fold peak increase at 12 hours (P < .005). Postoperative 12-hour B-type natriuretic peptide levels were associated with the duration of mechanical ventilation and the presence of a low cardiac output state after surgical intervention. On multivariate analysis, the 12-hour B-type natriuretic peptide level was an independent predictor of the duration of mechanical ventilation. In fact, B-type natriuretic peptide levels of greater than 540 pg/mL predicted mechanical ventilation beyond 48 hours, with a sensitivity of 88.9% and a specificity of 82.5%. In addition, B-type natriuretic peptide levels of greater than 815 pg/mL predicted the presence of a low cardiac output state within 48 hours after surgical intervention, with a sensitivity of 87.5% and a specificity of 90.2%. Conclusions: B-type natriuretic peptide determinations might be a useful tool for clinicians caring for infants and children after surgical intervention for congenital heart disease.