AIM: To compare the response of standard hepatitis B virus (HBV) vaccination between patients with chronic hepatitis C virus (HCV) infection and healthy individuals.METHODS: This is a prospective case-control study.A total of 38 patients with chronic HCV infection and 40 healthy controls were included. Vaccination was performed by injection of 20 μg recombinant HBsAg into the deltoid muscle at mo 0, 1 and 6. Anti-HBs concentration was determined 3 mo after the last dose and compared between the two groups. The response pattern was characterized as (1) high-response when the anti-HBs antibody titer was ＞ 100 IU/L, (2) low-response when the titer was 10-100 IU/L and (3) no-response when the titer was ＜ 10 IU/L.RESULTS: In the patient group, there were 10/38(26.3%) non-responders, 8/38 (21.1%)low-responders and 20/38 (52.6%) high-responders. The corresponding values in the control group were 2/40 (5.0%),7/40 (17.5%) and 31/40 (77.5%), respectively. The response pattern was statistically different between the two groups. In multivariate analysis, smoking was a significant confounder, while HCV infection lost its significant correlation with lower antibody response.CONCLUSION: Patients with chronic HCV infection tend to respond weakly to HBV vaccination compared to healthy individuals, though this correlation is not independent according to multivariate analysis.