Sound measurement of risk behaviors is essential to guide tailored risk reduction strategies as HIV infection patterns shift toward rural minorities, particularly in the southeastern United States where HIV disease remains highly stigmatized. Interactive Voice Response (IVR) systems appear to enhance reports of sensitive behaviors and can support telehealth applications to extend the reach of care in rural, underserved areas. This study evaluated the feasibility and data quality of an IVR telephone reporting system with rural substance users living with HIV/AIDS. Community-dwelling patients were recruited from a nonprofit HIV medical clinic in rural Alabama (N = 35 men, 19 women). Participants engaged in daily IVR reporting of substance use and sexual practices for up to 10 weeks. IVR reports were compared with retrospective Timeline Followback (TLFB) interview reports for the same period. IVR and TLFB reports showed good to excellent agreement for summary measures of alcohol consumption and sexual activity. Agreements for illicit drug use reports were less satisfactory. Reports of monetary spending on alcohol and drugs were significantly higher on the IVR. Most individuals showed good agreements for reports of day-to-day alcohol and drug use and sexual practices. The study established the utility of IVR assessment with rural, disadvantaged adults living with HIV/AIDS who are priority targets for risk reduction interventions. © 2011 American Psychological Association.