This study assessed 1,144 Brazilian injecting drug users (IDUs) recruited on the street through outreach syringe exchange programs by two multi-center cross-sectional studies: 287 IDUs were recruited during the AjUDE-Brasil I Pro- ject and 857 during the AjUDE-Brasil II Project. IDU characteristics related to drug use and sex- ual behavior, and legal and health conditions for the two studies were compared, using deci- sion tree and logistic regression for each indi- vidual study, with HIV infection as the outcome. Fifty-two percent of IDUs were HIV-infected in AjUDE I versus 36.5% in AjUDE II. In both stud- ies, HIV infection was independently associated with: mean background HIV prevalence for each site (OR = 2.17; 10.66), HCV seropositive status (OR = 19.79; 15.48), and men who report- ed ever having sex with other men (OR = 2.10; 2.09). Incarceration (OR = 1.41) and 8 or more years of injecting drug (OR = 2.13) were also associated with HIV in AjUDE II. The high HIV infection rates and high prevalence of both parenteral and sexual risk behaviors in the context of syringe-exchange programs are of great con- cern and demand thorough surveillance and renewed prevention strategies.