OBJECTIVES: The capacity for planning and implementing public health policies requires knowledge and understanding of population's health status. Information traditionally collected in population surveys is related to physical and biological measurements; however, the self-perception of health has recently gained importance. This has occurred in light of the widespread phenomenon of an aging population and increased prevalence of chronic diseases and disabilities at international level. The study compared the self-perception of health-related quality of life (HrQoL) of six Latin American countries and its relationship with socio-demographic variables. METHODS: This study was based on secondary data collected for World Health Survey 2005. Participating countries in the region were Brazil, Paraguay, Uruguay, Mexico, Dominican Republic and Ecuador. A probabilistic sample was collected for each country, with sex and age national representation (n=67,734). The study outcome was HrQoL classified in 5 categories (Very Good, Good, Moderate, Bad, Very Bad). Analyses to estimate the existence of real differences on overall HrQoL between countries were performed through binary and ordinal logistic regressions. Results were adjusted by sex, age and educational level. RESULTS: The two countries that reported the best HrQoL in Latin America were Uruguay and Paraguay. Brazil in contrast, reported the worst HrQoL, as it had the highest proportion of people reporting a poor or very poor health-status. When comparing HrQoL between countries using logistic regression, significant differences were found in the HrQOL for the 6 nations. Results persisted after adjusting for mentioned socio-demographic variables. CONCLUSIONS: Our study supported the usefulness and importance of measuring HrQoL and showed that real differences in self-perceived health exist between Latin American countries. Future research should consider cultural aspects like language, ethnicity or macro indicators such as unemployment rates or gross domestic product per capita in a multilevel analysis, for further understanding of HrQoL in Latin America.