Although the risk of hepatitis B virus (HBV) infection is high among people who use psychoactive substances, vaccination against this virus remains very limited. Our objective was to assess the level of vaccination coverage among these users, as well as the impact on this coverage of training provided to professionals in the Network of Medical Microstructures (RMS) in Alsace, which offers medical, psychological, and social care to users of psychoactive substances in general practitioners’ offices. In partnership with the Expert Service for the Control of Viral Hepatitis at the University Hospitals of Strasbourg (SELHVA), and as part of the 2009–2012 National Plan to Combat Hepatitis B and C, the RMS followed these users for 4 years (from 2009 to 2012). Following the training of healthcare professionals, vaccination coverage increased from 28% to 52% over 30 months (p<0.001). The results of an anonymous self-administered questionnaire sent to substance users and general practitioners in the network showed that, while the main modes of transmission are known, only 29% of substance users are fully aware of them. Vaccination is associated with awareness of the disease’s severity: among vaccinated users, 91% consider it potentially serious, versus 61% among unvaccinated users (p<0.001). (R.A.)