Catheter-related thrombotic and stenotic obstructions are the second most common serious complication of long-term total parenteral nutrition. Subsequent venous access problems have profound implications because of immediate and long-term requirements of nutrition support. Although improved understanding of pathogenesis has led to improved prophylaxis and treatment of thrombosis, some patients will have refractory obstructions that threaten venous access and lead to severe clinical sequelae, including superior vena cava (SVC) syndrome. We describe two cases of patients with SVC syndrome refractory to anticoagulant, thrombolytic, and balloon angioplasty therapy, managed successfully with percutaneous placement of expandable metal stents. A discussion of the current understanding of prophylaxis and treatment of catheter-related thrombosis and the role for interventional measures to restore venous patency and avoid permanent venous access problems accompanies the case descriptions.