The 20 μg (0-1-6 month) hepatitis B virus (HBV) vaccination is widely recommended for HBV vaccine-naïve immune adults in China. However, suboptimal protective responses may occur due to dose-series incompletion. We aim to investigate the immunogenicity of a 60 μg HB vaccine with a 0-2 month series among HBV vaccine-naïve immune adults aged 25-55 to assess potential alternative approaches for HB immunization. A two-center randomized controlled trial was carried out. Participants were randomly allocated to either the 20 μg (0-1-6 month) or the 60 μg (0-2 month) regimen. Blood samples were collected eight weeks after the final injection to measure the antibodies. A total of 583 adults (289 in the 20 μg regimen and 294 in the 60 μg regimen) were included. The seroprotection rates (SPRs) were 97.23% and 93.54% in the 20 μg and 60 μg regimens, respectively (p = 0.0261), and the geometric mean concentrations were 600.76 mIU/mL and 265.68 mIU/mL, respectively (p < 0.0001). The immunogenicity of the 60 μg regimen decreased significantly with age, particularly in adults aged 40 and older. The 60 μg regimen may be beneficial for adults under 40, especially those with poor compliance or in urgent need of immunization.