Antiretroviral therapy remains a challenge for persons living with HIV (PLWH), who must maintain high levels of adherence to prevent viral resistance and treatment failure. This effectiveness study examined a telephonic nursing program to translate well-validated cognitive-behavioral and motivational interviewing adherence counseling into routine clinical care. Participants were 98 PLWH who were followed for up to 6 months after recruitment from HIV care settings across the United States. Each participant received telephone counseling (Mdn =three sessions) from a trained nurse who followed up with the participant over time. Nurses assessed participants' readiness for adherence, provided support to overcome identified barriers, and offered information based on participants' questions. At 6 months after the start of treatment, a greater percentage of participants had adherence at or above 95% than expected for this population, based on a clinical interview. Self-efficacy was related to baseline medication adherence, whereas other clinical and demographic variables were not. Attrition was a concern but was unrelated to adherence, self-efficacy, or clinical severity measures. Telephone counseling was associated with a relatively high percentage of participants reaching target antiretroviral therapy adherence levels and may be an effective method to disseminate psychologically based counseling into a broad range of care settings.