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To determine if HIV/AIDS-specific quality of life (QOL) predicts adherence to antiretroviral therapy (ART).HIV-infected outpatients on efavirenz plus 2 or 3 nucleoside analogue reverse transcriptase inhibitors and with HIV viral loads <75 copies/mL were followed until the censoring event of detectable viremia or 1 year of follow-up. QOL was assessed at baseline with the HIV/AIDS-Targeted Quality of Life instrument (HAT-QoL), as were depression symptoms, stress levels, social support, and substance use. Follow-up high (≥95%) versus low (<95%) adherence was measured for 90 days before the censoring event.Fifty-six (48%) of 116 recruited participants had low adherence. Baseline financial worries (from the HAT-QoL) were greater in those with low versus high adherence (P = 0.02). Those with low versus high adherence also were more likely to use alcohol (P = 0.01) and other drugs (P = 0.02) currently at baseline. Regression analysis led to a model that included only current alcohol use (odds ratio [OR] = 2.65, 95% confidence interval [CI]: 1.20 to 5.87)) and financial worries (OR = 1.16, 95% CI: 1.03 to 1.310, for each 10-unit rise).Baseline financial worries were associated with antiretroviral adherence later in time. Questions about paying bills and financial ability to care for oneself may be clinically useful in identifying patients who will have suboptimal adherence.