BACKGROUND Approximately 5% of hepatitis B virus (HBV) carriers are coinfected with hepatitis D virus (HDV). HBV/HDV coinfection is a major cause of cirrhosis and end stage liver disease in chronic HBsAg carriers. The only approved therapy for chronic hepatitis delta is interferon alpha (IFN α) in either pegylated or conventional forms. Although higher doses and longer durations of IFN α therapy in HBV/HDV coinfected patients are currently applied, yet treatment response is low. OBJECTIVE We aimed to determine the efficacy of IFN α-2b therapy in patients with HBV/HDV coinfection. METHODS In this cross sectional study, 20 HBsAg carriers with positive Anti-HDVAb and RT-PCR for HDV RNA were recruited and treated for three year duration with 5 million units (MU) of IFN α-2b, three times weekly or one year with 5 MU of IFN α-2b daily. Sustained virological response (SVR) was defined as a negative qualitative HDV RT-PCR, 6 months after treatment cessation. RESULTS Overall, 3 (15%) subjects achieved SVR, 10 cases (50%) relapsed after treatment cessation and 7 (35%) patients did not clear HDV during the treatment. CONCLUSIONS HDV coinfection with HBV had very low response rate to high doses and long durations of IFN α-2b therapy.