Evidence showed that problematic drug users, in particular heroin users, have a higher risk of re-engagement in drug use and consequent death than the general population. Our aim was to perform a descriptive follow-up analysis to assess mortality and current drug use by reviewing over two decades of treatment admissions. We considered the cohort sample of heroin treatment-seeking patients from 1992 to 2013 that completed the clinical protocol (N= 627 patients). A total of 222 cases (35.4%) of heroin users were traced. A telephone post-treatment 22-year followup interview was then performed for each of these cases to allow assessment of current drug use in relation to mortality. The follow-up analysis estimated a percentage frequency of mortality of 13.1%, with attribution of the main cause of death revealing a connection with HIV/AIDS. Comparative analyses suggested the potential impact of some clinical conditions on drug-related mortality, namely, HIV infection, intravenous drug use, sharing of needles, unemployment and a greater number of years of heroin and other drug consumption when compared with the population of survivors. Among those who were alive, 17.4% reported that they had been using heroin and 15.5% cocaine in the previous 30 days. Our baseline and follow-up data confirm that around 10% of the heroin-addicted population presented a drinking problem. Our long-term study clearly shows the burden that HIV infection and intravenous drug use have imposed on the country in terms of mortality and morbidity. Moreover, the rate of alcohol and drug use over the follow-up period suggests that many aging heroin users are in need of continuous clinical attention.