Portal vein thrombosis has been considered idiopathic in 50% of cases reported in adults. Protein C deficiency is a recently described disorder characterized by a predisposition to develop thromboembolic disease. We report the findings in two patients with portal hypertension and bleeding varices due to portal vein thrombosis in whom a deficiency of protein C was present. Both cases were very similar, with a history of recurrent episodes of systemic thromboembolic disease, mesenteric venous thrombosis that required intestinal resection and upper gastrointestinal bleeding from gastroesophageal varices. Portal hypertension as well as portal vein thrombosis were demonstrated. The hematologic work-up revealed a deficiency of protein C. Both patients were subjected to the Sugiura procedure, and anticoagulation was instituted thereafter. At the time of surgery, a liver biopsy was performed, which was reported as "normal." Two years and 3 months, respectively, after surgery both patients are in good condition. We conclude that protein C deficiency should be investigated in all cases of portal vein thrombosis, especially in those with a history of thromboembolic disease elsewhere.