Human Immunodeficiency Virus (HIV) and substance use disorders can both significantly impact a patient's quality of life (QOL), and it is, therefore, important to assess QOL throughout treatments for these chronic conditions. This study evaluated the psychometric properties of the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) in 170 HIV-positive patients who participated in a substance abuse treatment study. Internal consistency of the FAHI was good. Convergent and discriminant validity were generally supported with comparisons to other patient-reported measures. FAHI scores were not significantly associated with viral loads or CD4 counts, and they were similar in patients with and without AIDS. Patients who achieved longer durations of drug and alcohol abstinence during treatment reported better QOL post-treatment. The FAHI appears to be a reliable and valid measure for assessing QOL in HIV-positive patients with concurrent drug and alcohol use disorders.