PURPOSE: To compare health-related quality of life (HR-QOL) in individuals infected with HIV to general population levels and to assess the relationship between HR-QOL and markers of disease progression in the era of highly active antiretroviral therapy (HAART). METHOD: This was a cross-sectional questionnaire-based study. This study included 154 individuals at least 18 years old with HIV who either were attending a London hospital or were visited by a community team in Brighton. Study participants were asked to complete two HR-QOL questionnaires. This study used HR-QOL, as measured using the Medical Outcome Study HIV Health Survey (MOS-HIV) and EuroQoL self-report (EQ-5D) questionnaires, as the main outcome measure. Responses on the EQ-5D were compared with a published general population data set. The relationships between scores on the MOS-HIV and EQ-5D questionnaires and a number of independent variables including CD4 count and viral load were also assessed. RESULTS: Each analysis was based on the results of at least 128 questionnaires. The mean MOS-HIV mental and physical component scores were 43.2 (SD = 12.2) and 41.8 (SD = 13.2), respectively. After adjusting for differences in age and gender, it was shown that individuals with HIV reported significantly lower EQ-5D(utility) ( p =.0001) and EQ-5D(VAS) ( p =.0001) compared with the general population. However, further analysis revealed few significant associations between markers of disease progression and HR-QOL. CONCLUSION: Individuals with HIV generally recorded significantly lower HR-QOL compared with the general population. Thus, prevention of further transmissions of the virus is still likely to prevent significant morbidity losses in addition to mortality losses, despite the availability of HAART. However, disease progression as measured is not clearly related to further reductions in HR-QOL.