Hepatitis B is a major health problem in China. However, little is known about the prevalence of hepatitis B virus (HBV) in Kaifeng, the major urban capital of Henan province, China. We found that HBV prevalence increased with age and that chronic HBV was predominant in adult males in Kaifeng. The HBV prevalence remained unchanged over a 5-year period for all age groups. Alarmingly, 25% of the population remained unvaccinated and potentially susceptible to future HBV infection. HBV immunization and health education initiatives should be carried out in this population to further reduce the overall prevalence of HBV.