Active injection drug use (IDU) is a behavior with the potential to offset healthcare engagement for those with HIV. At the Washington DC Veterans Affairs Medical Center, we identified 316 patients with a history of addiction during an 11-year period while actively engaged in routine visits to our HIV-primary care clinic. Among all IDU, active-abuse was determined in 141/316 (45 %). There were 120 clinically relevant blood stream infection (BSI) episodes. HIV/HCV co-infection (95 %) and use of antiretroviral therapy (76 %) were common at the time of BSI. The majority of BSIs occurred among those with active-IDU (72/120, 60 %). Active-IDU behavior was associated with more thrombotic disease (12 vs. 2 %, P = 0.001) and more frequent hospitalization (1.1/year ± 1.2 vs. 0.8/year ± 1.1, P = 0.03). When compared to drug-users with no active injection practices or those with remote IDU, active-IDU was associated with an increase in all-cause mortality (43 vs. 27 %, P = 0.003) and a decrease in age-adjusted survival (HR 1.7, CI 1.16–2.51, P = 0.007). Addressing addiction has the potential to impact avoidable medical complications and contribute to the continued, overall health of patients linked to HIV-care.