The aim of this investigation was to identify factors associated with HIV transmission risk behavior among HIV-positive women and men receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. Across 16 clinics, 1,890 HIV+ patients on ART completed a risk-focused audio computer-assisted self-interview upon enrolling in a prevention-with-positives intervention trial. Results demonstrated that 62 % of HIV-positive patients' recent unprotected sexual acts involved HIV-negative or HIV status unknown partners. For HIV-positive women, multivariable correlates of unprotected sex with HIV-negative or HIV status unknown partners were indicative of poor HIV prevention-related information and of sexual partnership-associated behavioral skills barriers. For HIV-positive men, multivariable correlates represented motivational barriers, characterized by negative condom attitudes and the experience of depressive symptomatology, as well as possible underlying information deficits. Findings suggest that interventions addressing gender-specific and culturally-relevant information, motivation, and behavioral skills barriers could help reduce HIV transmission risk behavior among HIV-positive South Africans.