Background Knowledge on Hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B (CHB) patients with long-term adefovir dipivoxil (ADV) treatment is limited. The aims of this study were to investigate HBsAg kinetics in patients with chronic hepatitis B virus (HBV) infection treated with long-term ADV and to evaluate different characteristics between patients with and without HBsAg loss. Methods We retrospectively evaluated HBsAg kinetics in 24 Chinese patients with chronic HBV infection who achieved continuous virologic suppression during ADV therapy. HBV genotype was determined at baseline. Liver biochemistry, hepatitis B e antigen status, serum HBV DNA, and HBsAg levels were measured at baseline, 6 months, and once every year thereafter. Results Of these 24 patients, 3, 1, and 20 patients were followed up for 3, 5, and 6 years, respectively. Baseline serum HBsAg level had a moderate correlation with baseline HBV DNA level (r=0.52, P=0.01). The median rate of HBsAg reduction during the therapy period was 0.08 lg IU·ml-1·y-1. Baseline serum HBsAg level was significantly higher than other time points (P ranges from 0.046 to 0.002). The HBsAg reduction rate during the first year was similar to that in other years (P>0.05). The HBsAg reduction rate during the first year in patients with eventual HBsAg loss was significantly faster than that in patients without HBsAg loss (P=0.005). Conclusions Serum HBsAg levels in Chinese CHB patients receiving long-term ADV demonstrated a gradual reduction. Patients with eventual HBsAg loss had a significantly faster HBsAg reduction rate during the first year than those without HBsAg loss.