Anthrax vaccine, adsorbed (AVA) is a vaccine containing aluminum hydroxide that is administered as six subcutaneous (s.q.) doses over 18 months. It is the only aluminum hydroxide licensed for s.q. administration. To optimize the vaccination schedule and route of administration, a prospective pilot study comparing the use of fewer doses administered intramuscularly (i.m.) as well as s.q. with the licensed schedule and route was performed. Data from that study on injection site reactions were extracted for this report. Erythema and induration occurred more commonly when the vaccine was administered s.q. compared to i.m. (P < 0.0001, P = 0.002, respectively). S.q. nodules were found only among the s.q. group (P < 0.0001). Erythema, induration and s.q. nodules were more common in women compared with men (P < 0.001) after the first s.q. dose of AVA dose. Reaction rates decreased when the interval between the first two doses of AVA was increased from 2 to 4 weeks.