In 2004, a hepatitis A outbreak occurred in Boston, Massachusetts with an incident rate of 14.8 per 100,000, compared to 4.2 in 2003. The majority of cases had risk factors of homelessness, injection drug use, or incarceration. In September 2004, the Boston Public Health Commission began an immunization campaign partnering with health centers, detoxification centers, homeless shelters, and our Emergency Department (ED) to increase the number of hepatitis A vaccinations and stem the epidemic. The ED rapidly developed (within days) a vaccination protocol. Hepatitis A vaccinations were offered to patients over age 21 years who were homeless, substance users, or incarcerated. From October 2004 through January 2005, the ED vaccinated 122 patients notable for 64% male, 61% homeless, 28% substance users, and 11% incarcerated. No reported vaccination reactions occurred. There was a 51% decrease in the number of cases of Hepatitis A in Boston in the first 4 months of 2005. As a partner, the ED helped stem the epidemic by rapidly providing vaccinations to those most vulnerable. This project provides a model for future collaborations between EDs and local, state, and federal organizations to address epidemics.