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To assess the relationship between N-terminal pro–brain natriuretic peptide (NT-proBNP) levels at different time points and early outcome, and to evaluate the reliability of NT-proBNP level as a predictor of early outcome after surgery in a large series of children with congenital heart disease (CHD).A retrospective observational study involving 363 consecutive children with CHD was used. Plasma NT-proBNP records were obtained for each patient before and 1, 12, and 36 hours after surgery. The specificity, sensitivity, and prediction value of NT-proBNP in predicting early postoperative outcomes were determined.Analyses confirmed that time-varying NT-proBNP level, particularly 1-hour postoperative levels, had prognostic value on the prediction of prolonged duration of mechanical ventilation, intensive care unit (ICU) stay, and inotropic therapy. Joint modeling analyses of a linear mixed effects model for NT-proBNP from before to 36 hours after surgery and generalized linear models for the duration of the mechanical ventilation, ICU stay, and inotropic therapy showed that a 1% increase in NT-proBNP was associated with 5.5%, 3.9%, and 3.5% relative increases in expected duration of mechanical ventilation, ICU stay, and inotropic therapy, respectively; related P values were .001, .001, and .01, respectively.After CHD surgery, the perioperative NT-proBNP levels might be powerful markers to identify subjects at higher risk for worse outcome.