We have observed six patients with life-threatening superior vena caval or pulmonary thrombosis after bidirectional superior cavopulmonary shunt. With the use of a case control study we sought to identify perioperative risk factors for this thrombotic complication. Medical records of six patients with cavopulmonary thrombosis and those of 24 patients in a control group were reviewed to abstract data for potential risk factors. Contingency tables and univariate logistic regression were used to determine associations between various perioperative parameters and occurrence of cavopulmonary thrombosis. Preoperative variables associated with thrombosis included bilateral superior vena cavae, odds ratio: 23, p = 0.02, increased age at surgery (p = 0.05), and female sex (odds ratio: 7, p = 0.05). The McGoon Ratio (index of relative pulmonary artery branch diameter) was inversely related to thrombosis risk (p = 0.08). Two torr increases in mean right atrial (p = 0.08) or ventricular end-diastolic (p = 0.05) pressures were associated with approximately 70% increases in thrombosis risk. Intraoperative prolongation of aortic cross-clamp time related directly to thrombosis risk (p = 0.06). Postoperative variables associated with thrombosis included increased superior vena caval pressure within 12 hours after surgery (odds ratio ≤ 10 for 5 torr increase in pressure, p = 0.02) and poor ventricular function (odds ratio: 9, p = 0.06). We conclude that high risk variables for patients undergoing a cavopulmonary shunt include bilateral superior vena cavae, female sex, increasing age, decreased McGoon Ratio, and elevated right atrial and ventricular end-diastolic pressure (before surgery), patients with prolonged aortic cross-clamp time (during surgery), and patients with elevated superior vena caval pressure and poor ventricular function (after surgery).