OBJECTIVE Although 48-week therapy with pegylated-interferons has been shown to be effective for the treatment of chronic hepatitis B (CHB), comparison of the efficacy of pegylated-interferon α-2a (Peg-IFNα-2a) and Peg-IFNα-2b in the therapy is not obvious. We aimed to compare the efficacy of Peg-IFNα-2a versus Peg-IFNα-2b in the treatment of CHB. METHODS Fifty-one CHB patients treated with 48 weeks of Peg-IFNα-2a (n=24) and Peg-IFNα-2b (n=27) who had been followed up between 2009 and 2011 at the Liver Clinic of Adana Numune Training and Research Hospital, Turkey, were investigated retrospectively. Six (25%) patients in the Peg-IFNα-2a group and nine (33%) in the Peg-IFNα-2b group were HBeAg-positive. Serum HBV-DNA, HBeAg, and HBsAg values were assessed at baseline. Biochemical and virological responses were evaluated every 12 weeks during the course of the treatment, at the end of the treatment, and follow-up week 24. Sustained virological response (SVR) was defined as sustained inhibition of viral replication (HBV-DNA<10 000 copies/ml) and a normal alanine aminotransaminase level until 24 weeks after treatment. Undetectable HBV-DNA was considered as less than 400 copies/ml. RESULTS Six of the 24 (25%) patients treated with Peg-IFNα-2a versus eight of the 27 (29.6%) patients treated with Peg-IFNα-2b achieved an SVR (P=0.75). HBeAg seroconversion occurred in three patients only in the Peg-IFNα-2b group. Rates of patients with undetectable HBV-DNA at 24 weeks after a 48-week course of therapy were 20.8% for Peg-IFNα-2a and 22.2% for Peg-IFNα-2b (P=0.82). CONCLUSIONS In CHB, there were no significant differences between Peg-IFNα-2a and Peg-IFNα-2b treatment groups in achieving an SVR and undetectable HBV-DNA levels.