Objective To evaluate the efficacy and safety of peginterferon alpha-2a (α-2a) for the elderly patients with chronic hepatitis B (CHB). Methods A total of 62 elderly CHB patients (age＞60 years) admitted in Wuhan Medical Treatment Center from April 2009 to April 2013 were recruited in this study and assigned into the elderly group. Another 65 CHB patients (age＜60 years) admitted during the same period were subjected to the control group. All the groups received a subcutaneous injection of α-2a at a dosage of 180 μg once per week for 48 consecutive weeks. Results The early virological responses (EVR) of HBeAg-positive and HBeAg-negative patients were significantly lower in the elderly group (4% and 5.4%) than in control group (25.92% and 21.05%), and so was the sustained virological response (SVR) in HBeAg-negative patients (28.00% vs 55.56%, P＜0.05). The HBeAg seroconversion rate was 32.00%(8/25) in the elderly group and was 33.33%(9/27) in the control group, without significant difference between them (P＞0.05). The incidence of main adverse effects, such as depression, ECG abnormalities and leucopenia, were significantly higher in the elderly group than in the control group (P＜0.05). Conclusion α-2a suppresses the replication of hepatitis B virus DNA, and results in HBeAg seroconversion in HBeAg-positive and -negative elderly CHB patients. It is more likely to achieve SVR to HBeAg-negative elderly patients. During the treatment, close attention should be paid to adverse reactions and timely intervention is necessary.