Purpose This study aims to investigate the antiviral effect of polyethylene glycol (PEG)-interferon α-2a and PEG-interferon α-2b treatment on hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) at the 48th week of treatment and the 24th and 48th week after withdrawal, in order to provide guidance on the antiviral treatment of HBeAg-positive CHB patients. Material and methods Antiviral treatment was performed on 155 HBeAg-positive CHB patients. Among these patients, 66 patients received PEG-interferon α-2a treatment and 89 patients received PEG-interferon α-2b treatment; and these treatments were administered by subcutaneous injection, once per week, which lasted for 48 weeks. Other antiviral and hepatoprotective drugs were not used during the treatment. Results At the 48th week of treatment, ALT recovery rate, HBsAg seroconversion rate, HBeAg seroconversion rate and HBV DNA titers dropped below 200 IU/mL rate were 69.7%, 6.1%, 27.3% and 50.0%, respectively, in the PEG-interferon α-2a group; and were 70.8%, 6.7%, 33.7% and 62.9%, respectively, in the PEG-interferon α-2b group. At the 24th and 48th week of follow-up after withdrawal, HBsAg seroconversion rate in these two groups did not change; and HBeAg seroconversion rate further increased. Furthermore, HBV DNA revealed a low recurrence rate. The difference between these two groups was not significantly significant. Conclusions PEG-interferon α-2a and PEG-interferon α-2b are effective antiviral drugs for the treatment of HBeAg-positive CHB, which has a HBsAg seroconversion rate of more than 5%. Furthermore, this sustained response effect was maintained at the 24th and 48th week of follow-up after withdrawal.