PURPOSE: To investigate time trends in health-related quality of life (HRQoL) in France and to report existing and changing demographic, socioeconomic, and geographic disparities. METHODS: Data were drawn from two independent national cross-sectional surveys conducted in 1995 and 2003, including 3,243 individuals aged 18–84 in 1995 and 22,743 in 2003. HRQoL was measured with the 8 subscales of the French version of the SF-36. RESULTS: After multiple linear regression, a significant decrease was observed between 1995 and 2003 in all scales scores, from −0.11 adjusted standard deviations for Social Functioning (95% CI: −0.15 to −0.08) to −0.23 for Vitality (−0.26 to −0.19). Increasing age, female gender, divorce/widowhood, lowest educational levels, chronic conditions, and living in the Northern region were identified as independent predictors of lower HRQoL scores. Testing interactions showed significantly greater differences between 1995 and 2003 for subjects aged 75–84 and for least educated subjects (Physical Functioning, General Health). The Gini index increased for all scales. CONCLUSIONS: We report evidence of worsening trends and possibly increasing demographic, socioeconomic, and regional disparities in HRQoL between 1995 and 2003 in France. Monitoring HRQoL in populations can provide unique and sensitive data, complementary to classical indicators based on mortality and morbidity.