While benefits of total parenteral nutrition (TPN) are well documented in a wide range of surgical conditions, deaths of two children secondary to mural thrombi from central venous catheters underscore the potential risks of such therapy. With the proven accuracy and widespread availability of echocardiography for diagnosis of mural thrombi, routine surveillance of all patients receiving TPN via central venous catheters is recommended, if fevers are present or if Candida is isolated on blood cultures. While treatment may involve surgical intervention, most mural thrombi will respond to thrombolytic agents. New approaches to long-term venous access are needed to prevent this lethal complication.