In recent years, France has witnessed both structural changes in the population of people living with HIV and a relative improvement in the social representation of HIV infection. However, potential changes in people’s day-to-day experience with HIV have not been documented. We used data from the national surveys ANRS-VESPA (2003) and VESPA2 (2011) to compare the levels and patterns of correlates of health-related quality of life (HRQL) in adult HIVinfected patients followed up in French hospitals over a period of eight years. Mean physical and mental SF-12 scores were compared (VESPA, n = 2072; and VESPA2, n = 2267) using analysis of variance (ANOVA) F tests. Heckman regression models were then used to identify independent correlates of physical and mental quality of life in the two surveys, while accounting for possible bias due to missing score values. A common set of potential socio-demographic, clinical, behavioral, and psychosocial correlates was tested. Individuals reported a decrease in physical quality of life in VESPA2 compared with VESPA (mean score (standard error): 47.5 (0.2) versus 49.6 (0.2), p < .0001), and better mental HRQL (44.3 (0.3) versus 42.3 (0.3), p < 0.0001). In both surveys, financial difficulties and patient-perceived experience of rejection behaviors by medical staff were independently associated with impaired physical and mental quality of life. Older age and unemployment were independently associated with impaired physical quality of life. Immigrants from Sub-Saharan Africa reported better mental quality of life. Findings show that quality of life levels in adult HIV-infected patients followed up at hospital in France has significantly, yet modestly, changed in recent years. However, the pattern of quality of life correlates has remained relatively stable. The impact of patient–provider relationships on self-reported outcomes is confirmed. Further research is needed to identify potential differences in quality of life correlates in specific subgroups of patients, such as men who have sex with men, women, immigrants, and injecting drug users.