Cost utility analysis is the most recommended pharmacoeconomic method since it allows widely comparison of cost-effectiveness results from different interventions. The method uses outcome of quality-adjusted life year (QALY) or disability-adjusted life year (DALY). Measurement of QALY requires the data of utility and life years gained. Utility is measured with the instrument for quality of life measurement such as EQ-5D. Recently, the EQ-5D is available in two versions which are EQ-5D-3L and EQ-5D-5L. This study aimed to compare the EQ-5D-3L and EQ-5D-5L to examine the most suitable version for Indonesian population. This study was an observational study employing cross sectional approach. Data of quality of life measured with EQ-5D-3L and EQ-5D-5L were collected from several groups of population which were respondent with chronic diseases, respondent with acute diseases, and respondent from general population (without illness) in Yogyakarta Municipality and Sleman District in Yogyakarta province, Indonesia. Convenience samples of hypertension patients (141), diabetes mellitus patients (178), and osteoarthritis patients (110), acute respiratory tract infection patients (204), cephalgia patients (120), dyspepsia patients (116), and respondent from general population (700) participated in this study. Responses on the 3L and 5L versions of EQ-5D were compared by examining the psychometric properties including agreement, internal consistency, ceiling effect, discriminatory power, and convergent validity. Based on psychometric properties tests of EQ-5D-3L and EQ-5D-5L, EQ-5D-5L tended to have better psychometric properties compared to EQ-5D-3L. Future studies for health-related quality of life (HRQOL) measurements for pharmacoeconomic studies in Indonesia should consider applying EQ-5D-5L.