Background: In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0 mu g/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B. Objective: This multicenter, randomized trial evaluated the safety and efficacy of regimens utilizing increased dose or treatment duration in treatment-naive Chinese patients with chronic hepatitis B. Study design: 670 HBeAg-positive patients from China, Malaysia, Taiwan area, Singapore, and Thailand were enrolled. Patients received PEG-IFN alfa-2b 1.0 mu g/kg/wk (arm A) or 1.5 mu g/kg/wk (arm B) for 24 weeks, or 1.5 mu g/kg/wk for 48 weeks (arm C). The primary end point was loss of HBeAg 24 weeks after end of treatment. Results: At the end of follow-up, HBeAg loss was significantly greater in arm C compared with arm A (31.3% vs. 17.3%; P = 0.001) and arm B (31.3% vs. 18.1%; P = 0.001). No significant difference in the rate of HBeAg loss was observed between arms A and B. The proportions of patients with HBe seroconversion, HBV DNA levels <20,000 IU/mL, and ALT normalization at the end of follow-up were significantly higher in arm C compared with arm A and arm B. In arms A, B, and C, rates of early treatment discontinuation were 6.3%, 4.9%, and 8.9%; of discontinuation due to an AE, 2%, 3%, and 3%; and of AEs requiring dose modification, 3%, 6%, and 10%, respectively. Conclusions: In Chinese patients with HBeAg-positive chronic hepatitis B, PEG-IFN alfa-2b 1.5 mu g/kg/wk for 48 weeks is more efficacious compared with 1.0 and 1.5 mu g/kg/wk for 24 weeks. (C) 2014 The Authors. Published by Elsevier B.V.