Background Despite CDC recommendations to vaccinate injection drug users (IDUs) against hepatitis A virus (HAV) and hepatitis B virus (HBV) infections, coverage remains low. Vaccination programs convenient to IDUs have not been widely implemented or evaluated. We assessed whether convenience and monetary incentives influenced uptake of free vaccine by 18–30-year-old IDUs in five U.S. cities. Methods IDUs recruited from community settings completed risk behavior self-interviews and testing for antibodies to HAV (anti-HAV) and hepatitis B core antigen (anti-HBc). Vaccine was offered presumptively at pre-test (except in Chicago); on-site availability and incentives for vaccination differed by site, creating a quasi-experimental design. Results Of 3181 participants, anti-HAV and anti-HBc seroprevalence was 19% and 23%, respectively. Although 83% of participants were willing to be vaccinated, only 36% received ≥1 dose, which varied by site: Baltimore (83%), Seattle (33%), Los Angeles (18%), New York (17%), and Chicago (2%). Participation was highest when vaccine was available immediately on-site and lowest when offered only after receiving results. Monetary incentives may have increased participation when on-site vaccination was not available. Conclusion IDUs were willing to be vaccinated but immediate, on-site availability was critical for uptake. Convenience should be a key consideration in designing strategies to increase vaccine coverage among IDUs.