Antiviral treatment of hepatitis C virus in thalassemia has raised concerns of ribavirin-induced hemolysis and increased iron loading. This study examined the change in liver iron concentration, transfusion requirement, virological response, and iron-related toxicities after pegylated interferon alpha-2a/ribavirin treatment in patients with thalassemia. Median transfusions increased by 44%. However, only 29% (4/14) of patients showed an increase of liver iron concentration > 5mg/g dry wt. and overall liver iron remained stable. One of 4 patients with genotype 2 or 3 demonstrated sustained viral response, compared with 50% with genotype 1 (6/12). No patient developed cardiac, liver or endocrine toxicities, although neutropenia occurred in 52%. The molar efficacy of deferoxamine improved with reduction in liver inflammation on biopsy (p=0.001). In conclusion, antiviral treatment is safe if transfusion requirement, iron toxicities and neutropenia are monitored.