Psychosocial and behavioral factors have been shown to be associated with adherence to highly active antiretroviral therapy (HAART) and treatment effectiveness. These factors have often been identified in selected populations through complex or time-consuming questionnaires. In this study we aimed at asking all the patients of a large population-based cohort receiving HAART a few short, explicit, and direct questions about these factors, and to examine the associations between their answers and prevalent treatment failure. All patients receiving HAART in western Denmark and central Copenhagen were offered participation. Participants answered a short, self-administered, anonymous questionnaire assessing psychosocial and behavioral factors and treatment adherence. Findings were linked with data on demographics, disease history, and treatment effect. Treatment failure was defined as two consecutive measurements of HIV-RNA above 400 copies per milliliter taken at least 14 days apart. Prevalence odds ratios were estimated by logistic regression. We found that a total of 887 of 1126 patients returned a completed questionnaire (response rate 79%). The overall rate of treatment failure in participants was 20%. Adjusted odds ratio estimates for treatment failure were 2.3 (confidence interval [CI] 1.3-4.3) for patients who stated poor treatment satisfaction, 2.1 (CI 1.2-3.7) for patients not fully disagreeing that they were depressed, and 2.8 (CI 1.5-5.4) for patients who stated to have been nonadherent within the preceding 4 days. Because of the cross-sectional nature of the study, causality could not be determined. These questions, however, may be relevant screening tools in clinical practice and in follow-up studies.