Objective To investigate the clinical efficacy of pegylated interferon α- 2a( PEG- IFNα- 2a) in the treatment of children with HBe Ag- positive chronic hepatitis B( CHB). Methods A total of 31 children with CHB aged from 2- 16 years were randomly enrolled in this study and divided into two groups based on the age: younger group( age 2- 6 years,n = 17) and older group( age 7- 16 years,n = 14). All patients were administered PEG- IFNα- 2a at the initial dose of 104 μg / m2/ week,which gradually increased to 135μg /week. The course of treatment ranged from 24 to 72 weeks. The indices including alanine aminotransferase( ALT),hepatitis B virus( HBV) DNA,HBV serological markers,and HBs Ag quantitative level were assayed at baseline and then regularly throughout the course of treatment. Treatment responses including biochemical,virological. and serological responses at different time points were compared between the two age groups. The safety of treatment and the relationship of treatment efficacy with age,course of treatment,and dynamics of HBs Ag quantitative level during treatment were analyzed. Normally distributed continuous data were analyzed by t test. Comparison of categorical data was made by χ2test. Results There were no significant differences in biochemical and virological responses at different time points between the two groups( all P > 0. 05). The HBs Ag clearance rate at week 24 of treatment was significantly higher in the younger group than in the older group( 41. 2% vs 7. 1%,χ2= 4. 644,P < 0. 05). The HBs Ag quantitative level declined more significantly in the younger group than in the older group at weeks 52 and 72 of treatment( both P < 0. 05). At week 52 of treatment,the HBV DNA clearance rate,HBe Ag clearance and seroconversion rates,and HBs Ag clearance and seroconversion rates in both groups increased,but no significant differences were found( all P > 0. 05). In patients whose treatment was extended to 72 weeks,the HBV DNA clearance rate and seroconversion rates of HBe Ag and HBs Ag were 100%,80%,and 60%,respectively. None of the 25 patients who finished the course of treatment experienced recurrence.Common adverse effects of interferon treatment were flu- like symptoms,changes in blood manifestation,and anorexia. No significant differences in body height and body weight were observed between the patients and normal children of the same age before and after the treatment.Conclusion PEG- IFNα- 2a is an appropriate treatment regimen for children with CHB. The treatment efficacy is related to the age of patients and the course of treatment. More prominent decrease in the HBs Ag quantitative level and higher HBs Ag clearance rate can be achieved in children of younger ages. Clinical efficacy can be improved with longer treatment. The change in HBs Ag quantitative levels has a predictive value for treatment outcomes. PEG- IFNα- 2a treatment is safe in children with CHB.