Universal hepatitis B (HB) vaccination among Thai newborns was initiated in 1992. The first dose of the monovalent HB vaccine was given at birth, then at months 2 and 6 simultaneously with the diphtheria-tetanus-pertussis whole-cell (DTPw) vaccine. In 2008, Thailand replaced the monovalent HB vaccine at months 2 and 6 with a combined DTP-HB given at months 2, 4, and 6, with an added monovalent HB vaccine at month 1 for infants whose mothers were HBV carriers. Despite this rigorous HB vaccination schedule, vaccinated infants who are now adolescents do not possess a protective level of anti-HB surface antigen (anti-HBs) (≥10 mIU/ml). Thus, many young adults may be rendered susceptible to HB infection. Our objective was to determine how HB booster vaccination may benefit high-risk adolescents. We evaluated the serological records of a cohort of medical students (n = 291), which showed that 271 students (93.1%) possessed anti-HBs less than the accepted protective level (<10 mIU/ml) and subsequently received the HB vaccine booster prior to medical school enrollment. We then examined the anti-HB surface antibody (anti-HBs) in 216 individuals six weeks after they were immunized. We found that 61%, 88%, and 94% of individuals with pre-booster anti-HBs of <1 mIU/ml, 1-<3 mIU/ml, and 3-<10 mIU/ml achieved protective anti-HBs, respectively. Post-booster geometric mean titers were 305, 513, and 1,929 mIU/ml in these groups and correlated with pre-booster anti-HBs titers. These data suggest that medical students with known anti-HBs <1 mIU/ml will benefit from 3 doses of HB vaccine at 0, 1, and 6 months. Students with anti-HBs 1-<10 mIU/ml would benefit from an HB vaccine booster without further anti-HBs evaluation.