OBJECTIVE: To determine whether procalcitonin discriminates between postcardiopulmonary bypass inflammatory syndrome and infectious complication in children better than does C-reactive protein. DESIGN: Prospective study of children admitted to the intensive care unit after cardiopulmonary bypass. PATIENTS: Classified according to a diagnosis of systemic inflammatory response syndrome and bacterial infection or systemic inflammatory response syndrome but no bacterial infection. Two hundred thirty-one cases were recruited. MEASUREMENT AND MAIN RESULTS: Procalcitonin, C-reactive protein, and leukocyte count were measured daily from surgery until day 3. Twenty-two patients were infected (9.5%). Significant differences were detected in the procalcitonin values of the infected group vs. the noninfected group, especially at day 2 (p = .000). There were no differences in the C-reactive protein values. The optimal cutoff for procalcitonin was >2 ng/mL at day 1 and above 4 ng/mL at the day 2. There was a greater sensitivity and specificity than with C-reactive protein as an infection predictor. CONCLUSION: Procalcitonin is useful in the diagnosis of bacterial infection after cardiopulmonary bypass. Because procalcitonin kinetics are different in postcardiopulmonary bypass patients, the cutoff to diagnose infection should be different from the normal cutoff.