Hepatitis B virus (HBV) vaccination is recommended for health-care professionals because of their frequent contact with blood. At one medical school, new students undergo HBV antibody tests upon admission, and antibody-negative individuals receive the HBV vaccine. We aimed to characterize individuals who remained antibody negative after HBV vaccination. Between 2009 and 2017, we enrolled 1064 first-year students from a medical school where their HBV antibody test and vaccination records remained. We analyzed data regarding the hepatitis B surface antibody (anti-HBs) test record during admission, vaccination record for antibody-negative participants, anti-HBs test result after completing the three vaccination doses, drug name of the vaccine used, sex, body mass index (BMI), and age. We calculated the yearly percentage of antibody-negative individuals and analyzed the characteristics of vaccine-refractory cases by logistic regression analysis. Of the 1064 participants, 999 were initially antibody negative. They were vaccinated with HBV thrice and tested for antibodies after vaccination. The average age of participants was 20.1 y, with 677 males. Although the type of vaccine has been changed since 2016, the average rate of refractoriness from 2009 to 2015 was 6.9% per year and 18.6% after 2016. Logistic regression analyses showed that sex (male vs. female; OR, 1.787), BMI (OR. 1.171), and vaccine type (genotype A vs. genotype C: OR, 3.144) were significant factors associated with antibody-negative individuals. Vaccine type differences altered the proportion of antibody-refractory individuals, with no association with age. The data on vaccine refractoriness will be continuously analyzed in the future while considering other factors.