We developed a scale among HIV-positive injection drug users (IDUs) to measure self-perceived responsibility to limit HIV transmission during sex. We describe the characteristics of HIV-positive IDUs (n=1114, 62% male, HIV-positive for 9 years on average) who felt responsible for protecting their sexual partners from HIV and evaluated whether such feelings were associated with safer sexual practices. Using this scale (Cronbach alpha=0.83) and audio computer-assisted self-interviewing technology, 75% of this sample felt responsible for protecting their sexual partners from HIV. In cross-sectional multivariate analysis, HIV-positive IDUs who felt responsible were those with greater HIV knowledge (adjusted odds ratio [95% confidence interval]: 1.74 [1.26 to 2.40]), perceived social support (1.77 [1.28 to 2.44]), self-efficacy for safely injecting (1.41 [1.02 to 1.94]), and self-efficacy for using condoms (1.92 [1.38 to 2.68]). Feeling responsible was associated with having relatively fewer sex partners (<10 vs. >or=10, 0.57 [0.34 to 0.96]) and a lower odds of unprotected sex (0.63 [0.45 to 0.89]) but was not associated with safer injection practices. Feelings of responsibility did not vary by demographic characteristics, suggesting that prevention messages that encourage HIV-positive people to play a role in curbing HIV transmission may be acceptable to many HIV-positive IDUs. Working with HIV-positive IDUs to increase or reinforce feelings of responsibility may reduce the sexual transmission of HIV.