Objective: Brazil accounts for ;70% of injection drug users (IDUs) receiving highly active antiretroviral therapy (HAART) in low-income/middle-income countries. We evaluated the impact of HAART availability/access on AIDS-related mortality among IDUs versus men who have sex with men (MSM). Design: Nation-wide analysis on Brazilian IDU and MSM diagnosed with AIDS in 2000–2006. Methods: Four national information systems were linked, and Cox regression was used to assess impact of HAART availability/access on differential AIDS-related mortality. Results: Among 28,426 patients, 6777 died during 87,792 personyears of follow-up. Compared with MSM, IDU were significantly less likely to be receiving HAART, to have ever had determinations for CD4 or viral load. After controlling for confounders, IDU had a significantly higher risk of death (adjusted hazard ratio: 1.94; 95% confidence interval: 1.84 to 2.05). Among the subset that had at least 1 CD4 and viral load determination, higher risk of death among IDU persisted (hazard ratio: 1.82; 95% confidence interval: 1.58 to 2.11). Nonwhite ethnicity significantly increased this risk, whereas prompt HAART uptake after AIDS diagnosis reduced the risk of death. After controlling for spatially correlated survival data, AIDS-related mortality remained higher in IDU than in MSM. Conclusions: Despite free/universal HAART access, differential AIDS-related mortality exists in Brazil. Efforts are needed to identify and eliminate these health disparities.