Background: The World Health Organization Quality of Life Questionnaire (WHOQOL)-BREF is one of the most known general questionnaires for assessment of quality of life (QOL) in both healthy populations and in various diseases subgroups. The aim of the present study was to examine the construct validity of this questionnaire in patients with coronary artery disease (CAD) using factor analysis. Methods: Two hundred and seventy-five patients aged 35-80 years old with the diagnosis of CAD admitted to the Tehran Heart Center operating room for coronary artery bypass were consecutively entered into the study. QOL was assessed using the WHOQOL-BREF. To estimate the reliability of the QOL questionnaire, Cronbach's a coefficient was measured. To assess the structure of the questionnaire, we firstly performed confirmatory factor analysis to test the hypothesized factor models. Exploratory factor analysis was then performed using the principal component method with varimax rotation. Results: Reliability of the questionnaire was low (Cronbach's a for different domains ranged from 0.24 to 0.74). In confirmatory factor analysis, only the 1-factor model indicated a good fit to the data. The exploratory factor analysis indicated a five-factor solution that jointly accounted for 55.7% of the variance observed. Also, the pattern of item loading was very different from the original structure of the questionnaire. Conclusions: The findings suggest that the WHOQOL-BREF might only be a measure of the overall QOL in patients with CAD, and is not a suitable instrument for measuring the different QOL dimensions as expected in this population.