Background: Hepatitis B infection and resulting health sequela is a worldwide health problem. Adults at increased risk of infection are recommended to receive hepatitis B vaccine for protection, followed by postvaccination titer testing to confirm immunity. The aim of this study is to assess coverage rate and immunologic response to hepatitis B vaccine and factors influencing seroreactivity. Methods: This was a cross-sectional study carried out among medical doctors of Makkah city, medical interns, and medical students of Umm Al-Qura University, Saudi Arabia. A self-administered questionnaire was used to collect data for evaluation of hepatitis B vaccination coverage, immune status, and associated risk factors. Results: Three hundred twenty-one (79.9%) out of 402 participants received the vaccination. Of those vaccinated 159 (48.3%) had subsequent testing for anti-HBs. One hundred thirty-nine (87.4%) had an appropriate immunologic response to the vaccine (titer >= 10 mIU/mL). Factors negatively influencing seroreactivity were male gender, high BMI, smoking, incomplete vaccination series, vaccination schedule non-adherence, and long elapsed time since last vaccination; with p-values of 0.001, 0.000, 0.002, 0.001, 0.037, and 0.000, respectively. Conclusions: Hep B vaccination coverage in our study is considered insufficient. Smoking and obesity were modifiable and preventable risk factors negatively affecting the immunologic response. The development and enforcement of better health policies aimed at increasing access and coverage of the HBV vaccination of at-risk populations like medical students, with increased awareness, is recommended.