Street-based sex-work and poly-substance drug use, coupled with low vaccination rates and limited utilization of the mainstream health care system, put the sex worker communities of Bogotá’s city center at extreme risk of infection with the hepatitis B virus (HBV). Vaccination is critical to maintaining low prevalence of the disease and low incidence of new cases, yet the floating and inconsistent nature of Bogotá’s drug-involved female and transsexual prostitution communities make it difficult to complete a 3-dose vaccination program. Between December 2011 and March of 2012, the Fénix Foundation collaborated with the Bogotá Health Department to deliver free HBV vaccines to this vulnerable population. This paper outlines methods used in the vaccination program to generate a 37.7 % adherence rate, significantly higher than that previously reported for HBV vaccination programs also targeting marginalized populations. This program’s practices are based on the Fénix peer leader method, and are offered as a model that can be applied to other health interventions operating in analogous contexts, with similarly high-risk populations.