The combination of pegylated interferon and ribavirin is the first option treatment for chronic hepatitis C (HCC). Although not frequent, several vascular adverse events, such as Raynaud's phenomenon, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome and central retinal vein occlusion, have been associated with the use of pegylated and standard interferon. We report the cases of two patients with HCC who, while receiving treatment with pegylated interferon and ribavirin, developed decompensated liver disease. Radiological tests revealed acute portal thrombosis. After the diagnosis was established, anticoagulant therapy was started, which resolved the portal thrombosis.