- Data on efficacy, safety, and durability of intradermal vaccine administration in persons who have not responded well to intramuscular administration of hepatitis B virus (HBV) vaccine are relatively scarce. We designed a prospective case series in an urban tertiary care hospital in Israel. The medical records of 4,007 healthcare personnel who had worked in the hospital between 1996 and 2006 were examined and those with an unsatisfactory level (<10 mIU/mL) of hepatitis B surface antibody (HBsAb) following two courses of a three-dose intramuscular HBV vaccine ("nonresponders") were identified. They were vaccinated with three doses of 5 micrograms of intradermal recombinant HBs antigen (HBsAg)-based vaccine at weeks 0, 2, and 4. Level of HBsAb was determined four weeks after the last dose and an additional dose was administered as needed. HBsAb level was again determined 24 weeks after the final vaccine dose to assess late immune reactivity and long-term durability of the vaccine. Vaccine safety was assessed at each vaccination and testing session. Twenty-seven subjects were included in the study, and 21 completed the study. The proportion of subjects with satisfactory HBsAb level at four weeks after the last administered dose was 70.3% (19/27). The proportion of subjects with sustained immune response at 24 weeks was 62.9% (17/27) according to intention-to-treat analysis and 80.9% (17/21) according to per-protocol analysis. There were no reports of adverse events in response to the administration of the vaccine. Intradermal administration of HBV vaccine offers an efficient, safe, and durable option for intramuscular vaccine nonresponders, and represents a means to optimize utilization of the wide-spread HBsAg-based vaccine formulation. This article is protected by copyright. All rights reserved.