Introduction <p> We aimed to determine the antibody response of intradermal (ID) plus intramuscular (IM) recombinant hepatitis B vaccination in individuals with inadequate immune response despite vaccination.</p> Methods <p> This single-center, retrospective study included individuals aged ≥18 years who had previously completed the primary 3-dose vaccination course for hepatitis B and had anti-HBs titers &lt;10 mlU/ml. Participants were administered a double dose of recombinant hepatitis B vaccine (5 microgram ID+35 microgram IM) at months 0, 1, and 6. Quantitative anti-HBs titers were assessed at months 2 and 7. Vaccination response was categorized as unresponsive (anti-HBs&lt;10 mlU/ml), weak (anti-HBs=10-100 mlU/ml), moderate (anti-HBs=101-1000 mlU/ml), and strong (anti-HBs&gt;1000 mlU/ml).</p> Results <p> A total of 43 individuals were included. After the 2nd and 3rd doses of vaccination, protective antibody responses (anti-HBs&gt;10 mlU/ml) were obtained 81.3% (27.9% weak response, 16.3% moderate response, 37.2% strong response) and 93% (16.3% weak response, 27.9% moderate response, 48.8% strong response), respectively. Anti-HBs antibody titers increased from 505±501 in the 2nd vaccination to 666±469 in the 3rd vaccination (p=0.003). After the 3rd dose of vaccination, protective antibody responses inreased from 86.7% to 100% in PLwHIV, from 69.2% to 76.9% in patients with rheumatic diseases, and from 91.7% to 100% in immunocompetent individuals compared to the second dose of vaccination. No antibody response was achieved in any of the patients using rituximab.</p> Conclusion <p> ID (5 µg) plus IM (35 µg) recombinant hepatitis B vaccine is promising as an alternative vaccination method in various specific populations, which unresponsive to standard vaccination, such as PLwHIV, immunocompetent patients, and immunomodulator users.</p>