To evaluate the incidence, mortality, late outcome, and cause of central venous thrombosis after pediatric heart operations and other operations performed with cardiopulmonary bypass, we identified patients with postoperative central venous thrombosis during a 10-year period at a single pediatric hospital. There had been 1591 open heart (with bypass) and 1086 closed heart (no bypass) procedures and 13 operations with cardiopulmonary bypass for extracardiac indications. There were 20 patients with central venous thrombosis, yielding incidences of 1.1% and 0.2% after cardiopulmonary bypass and after closed heart operations, respectively. When neonates were compared with older children (1 to 119 months of age) undergoing heart procedures, a tenfold increase (5.8% vs 0.6%) (p < 0.001) in the incidence of central venous thrombosis was observed. The mortality was eight of 20 (40%). Central venous thrombosis contributed to seven deaths and it was a direct cause of one death. Ten patients were reinvestigated 5 to 108 months after central venous thrombosis. The outcome of surgery was excellent in eight. Two had residual thrombosis, but this was not hemodynamically significant to the cardiorespiratory condition of the patients. During or preceding thrombosis, low levels of antithrombin III and/or protein C and high levels of the plasminogen activator inhibitor were observed in five of the patients. A congenital thrombotic risk factor, "resistance to activated protein C," was found in two of 12 tested patients with central venous thrombosis (17%). In conclusion, central venous thrombosis, especially in neonates, is an important cause of morbidity and mortality after cardiac operations. The cause is multifactorial, with contributions from multiple acquired thrombophilic coagulation abnormalities, and resistance to activated protein C may act as a risk factor for thrombosis already during neonatal period.