Acute disruption of venous return during cardiopulmonary bypass (CPB) may be due to malposition of the venous cannula, kinks or obstruction of the venous tubing by a smaller cannula, airlock, or mechanical disruption of blood flow. We describe an acute obstruction of the venous cannula by blood clots that were visualized on the transesophageal echocardiogram during CPB. Appropriate measures were taken by the surgeon to evacuate the clot and restore CPB. The clots were not seen on the transesophageal echocardiogram before CPB raising suspicion that they originated in a lower extremity and migrated to the right atrium resulting in venous cannula obstruction.