Audio computer-assisted self-interviewing (A-CASI) is now widely used to gather information from many types of research participants, including injection drug users (IDUs). The purpose of this study was to describe how HIV-positive IDUs participating in an intervention trial viewed A-CASI and to identify the characteristics of participants who held unfavorable attitudes toward A-CASI. Using a sample of participants who completed 12-month assessments (n=821), we found that most (>80%) of the sample held favorable or neutral attitudes toward A-CASI. Approximately 18% said that they would prefer an interview with a person to a computer, 12% said that they did not understand the questions they heard on the computer, and 14% said that the computer made it hard to be open and honest about risk behavior. Multivariate analyses found that participants who were more socially marginalized (with unstable housing and lower sense of empowerment) and had greater physical limitations and lower CD4 cell counts were consistently more likely to report various negative A-CASI attitudes; however, some outcome-specific findings were also noted. Our research supports the feasibility and general acceptability of A-CASI with HIV-positive IDUs, and it suggests further research exploring the associations between A-CASI attitudes and characteristics of disadvantaged populations.