Background and Aim: In 1991, the world health organization initiated a project to simultaneously develop an instrument for measuring quality of life in 15 countries. The study yielded two questionnaires, namely WHOQOL-100 and WHOQOL-BREF. These were intended as generic QOL measurement tools to be used in a broad range of diseases, for different degrees of disease severity, and in various cultural subgroups. The objective of the current study was to evaluate the Iranian version of the WHOQOL-BREF. This 26-item instrument comprises four domains: Physical Health, Psychological, Social Relationship, Environment and the overall QOL/health.Material and Methods: We administered the questionnaire to 1167 adults in Tehran. The stratified sample consisted of 476 diseased subjects and 700 healthy ones. We tested the instrument's reliability (internal consistency, test-retest), discriminate validity and factorial structure.Results: The participants had an age mean of 36.3 years (SD=13.2) and had an average 11.5 years of education. Using Cronbach's a. and intraclass correlation, all domains met the minimum reliability standards, with the exception of social relationship domain (a=0.55). The latter could be attributed the small number of questions in this domain and the sensitive nature of the questions themselves. Since 83% of the questions show maximum correlation with their original domain, the factorial structure of the questionnaire was regarded as acceptable. The questionnaire has the ability to discriminate different groups after adjustment for confounding factors in regression analysis.Conclusion: This study demonstrated good to excellent reliability and acceptable validity in various groups of subjects in Iran. The instrument may be used in future studies, albeit with minor modifications in the domain of social relations, as determined by expert opinion.