A cross sectional study looked at the association between sociodemographic factors, HIV/AIDS clinical history and health-related quality of life (QOL) in HIV/AIDS persons. It used the WHOQOL-BREF-THAI questionnaire completed by 3,596 patients during 2008 in three Thai hospitals. The questionnaire explored five QOL domains: Physical, Psychological, Social, Environment and Overall and it was for the first time administered to many HIV/AIDS patients in Thailand. Descriptive statistics and inferential statics (bivariate and multivariate : one-way ANOVA, Kruskal-Wallis Test, Pearson Correlation and independent ttest)) were used to test association between independent factors and QOL. Results: The following associations were all statistically significant. Males had higher QOL than females in Physical, Psychological and Overall domains. Younger age was associated with higher QOL in Physical and Social domains, older age in Psychological and Environment domains. Married had higher psychological QOL than single and separated. Good adherence to, more than 3 year duration of ARV treatment and not suffering AIDS related events were associated with higher QOL in all except social domains. VL <50 copies/ml had higher QOL in all domains except social and environment domain. Higher education, high income and more than 200 CD4+ cell per mm3 had higher QOL in all domains. Conclusion: Thai HIV/AIDS persons have health-related moderate to high QOL comparable similar person from high income countries. This is mainly due to similarities in some socio-demographic characteristics, free availability of and adherence to ARV, accessibility to other of HIV/AIDS care components. The WHOQOL-BREF-THAI questionnaire is an appropriate instrument to measure QOL in Thai HIV/AIDS persons.