Thrombosis in extracorporeal membrane oxygenation (ECMO) circuits remains a frequent complication. We characterize the location, extent, structure, and clinical implications of thrombi in 53 ECMO circuits from 46 pediatric patients. The tubing, pump, and oxygenator were examined for visible thrombi. Representative samples of thrombi were collected for histologic, immunofluorescence, and immunohistochemical analysis. Thrombi were found in 81% of ECMO circuits. The most clinically significant were inflow oxygenator membrane surface thrombi (11% of circuits), arterial tubing thrombi (30%), and venous tubing (26%) or connector thrombi (26%). Oxygenator membrane surface thrombi resulted in rapidly increasing delta pressure across the oxygenator over 1–2 days, oxygenator failure, and circuit replacement. Oxygenator membrane surface thrombi were associated with intravascular venous thrombosis and bacterial infection before starting ECMO. Arterial cannula/tubing thrombi led in one case to aortic and mesenteric artery thrombosis followed by bowel infarction. In 11% of cases, venous tubing thrombi grew large enough to break off and embolize to the pump, resulting in increased hemolysis. Antifibrinolytic therapy during ECMO was associated with an increased risk of pump thromboembolism. Other less clinically significant thrombi included pump axle thrombi with thrombus fragments trapped in the oxygenator (45%), and deep oxygenator membrane thrombi (15%). Examination of ECMO circuits after removal is a useful quality improvement tool that can elucidate the cause of circuit problems, indicate patients at increased risk of thrombosis, and suggest areas for possible improvements.