We investigated the characteristics of human immunodeficiency virus (HIV)-positive injection drug-using women who reported unprotected vaginal and/or anal sex with HIV-negative or unknown serostatus (serodiscordant) male partners. Of 426 female study participants, 370 were sexually active. Of these women, 39% (144/370) and 40% (148/370) reported vaginal and/or anal sex with serodiscordant main and casual partners, respectively. Sixty percent of women inconsistently used condoms with their serodiscordant main partners, whereas 53% did so with casual partners. In multivariate analysis, during sex with main partners, inconsistent condom users were less likely to feel confident about achieving safe sex (self-efficacy), personal responsibility for limiting HIV transmission, and that their partner supported safe sex. Inconsistent condom use was also more likely among women who held negative beliefs about condoms and in couplings without mutual disclosure of HIV status. Regarding sex with casual partners, inconsistent condom users were more likely to experience psychologic distress, engage in sex trading, but they were less likely to feel confident about achieving safe sex. These findings suggest that there are widespread opportunities for the sexual transmission of HIV from drug-using women to HIV-uninfected men, and that reasons vary by type of partnership. Multifaceted interventions that address personal, dyadic, and addiction problems are needed for HIV-positive injection drug-using women.