It is uncertain whether immunologic memory persists for 15 years or more after immunization and whether the efficacy of universal hepatitis B vaccination program (UHBVP) in socio-economically disadvantaged area with hyperendemicity of hepatitis B virus (HBV) infection is similar. We assayed hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) on 2839 students aged 15 years or more born before (N = 248) and after (N = 2591) UHBVP. We found that students born after UHBVP had significantly lower positive rate of anti-HBs than those born before UHBVP (44.6% versus 75.0%, p<0.0001). Seropositive rate of HBsAg for students born after UHBVP was also declined significantly (1.9% versus 9.3%, p<0.0001). Preventive fraction of UHBVP on HBsAg-seropositivity was 78% (95% confidence interval, 0.64-0.87), which was at least 10% lower than previous studies. Preventive fraction in Han Chinese (74%) and Atayal (78%) students were lower than Amis students (94%). In 2264 Han Chinese students, preventive fraction was 16% lower in those resided in rural than urban areas. These observations indicated that UHBVP was less effective in socio-economically disadvantaged area where HBV infection was hyperendemic and the long-term efficacy and immunogenicity of vaccination were modified by host factors and factors associated with urbanization.