Deferiprone (L1) is an orally active iron-chelation agent that is being evaluated as a treatment for iron overload in thalassemia major. Although some reports have concluded that L1 may exacerbate hepatic fibrosis and the deterioration of liver function in thalassemia patients, other studies have reported no detrimental effects. In view of these serious concerns regarding the hepatic toxicity of L1, a Taiwanese group of β-thalassemia (thal) patients with the longest known duration of L1 therapy and who had provided liver biopsies, were enrolled in this study. From April 1999 to July 2004, the 17 enrolled thalassemia major patients had been on L1 therapy for as long as 19 to 60 months. Two liver biopsies from each of the 17 patients were received at the China Medical University Hospital, Taichung Taiwan. Serum alanine aminotransferase (ALT), viral serological studies for hepatitis B and hepatitis C, iron scores and fibrosis scores were available at the beginning of the study and at the time of the second biopsy. Overall, the 17 patients received L1 therapy continuously for a mean period of 3.3 years. With the exception of two patients, fibrosis scores decreased in all patients after therapy. Three patients had increased iron scores after therapy of L1 and 11 patients had increased ALT levels; increased ALT levels occurred more frequently in hepatitis C positive patients. In this study, most thalassemia major patients had no progression of hepatic fibrosis or increased liver iron stores during long-term L1 therapy.