The prevalence of anti-retroviral therapy (ART) use over time and the incidence of AIDS in a cohort of HIV-seroconverting injecting drug users (IDUs) were assessed by means of a hospital-based study of IDUs with a well documented date of HIV infection. Use of ART and clinical endpoints were assessed by hospital records. Three calendar periods (before 1992, 1992–6 and 1997–2000) were defined as corresponding to modalities of ART available. Prevalence of ART usage in each calendar period, changes in medication and, hazard of AIDS in patients reaching the same duration of HIV infection at different calendar periods were analysed. In total, 132 IDUs with a median age of 23 years at seroconversion were followed up for 6.8 years (median) (range 0.2–15.7). At the end of the study, 58 patients (44%) had developed AIDS. Before the introduction of highly active anti-retroviral therapy (HAART) 12% of patients were on ART. Starting in 1997, an increasing proportion were receiving HAART with a prevalence of 39.5% by January 2000. Taking 1992–6 as the reference category the relative hazard of AIDS during 1997–2000 was 0.42 (95% CI, 0.1–1.1) (P = 0.09). A 40% penetration of HAART in a cohort of IDUs with known dates of seroconversion resulted in a 58% reduction of the hazard of AIDS.