The aim of this study was to elucidate the long-term outcome after interferon (IFN) or lamivudine (LMV) treatment in Japanese patients with hepatitis B e antigen (HBeAg) positive chronic hepatitis B. Inclusion criteria were biopsy proven chronic hepatitis or liver cirrhosis, no history of IFN or LMV treatment. Three hundred twenty-seven patients satisfied above criteria were treated with IFN or LMV. The primary end point of our study was serum clearance of HBeAg and decrease of serum HBV-DNA to ≤5 LEG/ml after the initiation of treatment. This study was a retrospective cohort study. Attainment of serum clearance of HBeAg and decrease of serum HBV-DNA to ≤5 LEG/ml was regarded as response. Two hundred eighty-six patients had got response after the initiation of treatment. The cumulative rate of response was 28.0% in the first year, 56.2% at the 5th year and 82.5% at the 10th year. Response occurred when HBV-DNA load was high level of more than 7 LEG/ml, and serum ALT level was more than 100 IU/L, HBV genotype was B. IFN and LMV were the similar effect on response (P = 0.410). On IFN therapy, cumulative rate of response in patients of <35 years was higher than that in patients ≥35 years (P = 0.002). Our results suggest that (1) IFN and LMV are the similar effect on response, (2) IFN therapy is more effective for younger patients. J. Med. Virol. 79:1286–1292, 2007. © Wiley-Liss, Inc.