Objective: To determine whether health-related decision-making is disrupted in HIV-associated neurocognitive disorders (HAND). Method: The study sample included 43 HIV+ individuals with HAND (HAND+), 50 HIV+ individuals without HAND (HAND−), and 42 HIV- participants who were recruited from local HIV clinics and the San Diego community. Participants were administered two measures of health-related decision-making as part of a comprehensive neurocognitive, health literacy, psychiatric, and medical research battery: 1) The Decisional Conflict Scale (DCS), which measures self-efficacy related to a medical treatment decision scenario and 2) The Modified UCSD Brief Assessment for Capacity to Consent (UBACC-T), which measures comprehension of an end of life treatment decision scenario. Results: Multiple linear regression analyses controlling for group-wise demographic and psychiatric differences revealed that HAND group was an independent, unique predictor of performance on both health-related decision-making measures (ps < .05). Specifically, the HAND+ sample evidenced significantly poorer scores than both comparison groups on both the DCS and the UBACC-T (Cohen's d range .52−.78). Within the HIV+ sample, poorer health-related decision-making impairment was associated with worse performance on tests of episodic memory, attention/working memory, risky decision-making (i.e., Iowa Gambling Task), and health literacy (ps < .05). Conclusion: Findings indicate that individuals with HIV-associated neurocognitive disorders evidence moderate deficits in the complex process of effectively comprehending and evaluating the pros and cons of various health-related choices in order make an informed treatment decision. Further evaluation of the neurobiological correlates, neural substrates, and clinical health outcomes associated with health-related decision-making in HIV disease is warranted.