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Background: Preference-based Health-Related Quality of Life (HRQL) is one of the most important indicators for calculating QALY (Quality-Adjusted Life Years) in a cost-effectiveness analysis. This study aimed to collect data on healthy individuals' HRQL based on the preferences of Japanese people who had undergone a comprehensive health check-up, and to examine the influence of relevant factors, such as blood biochemical data and lifestyle behavior.Methods: We conducted a cross-sectional study targeting people who had undergone a comprehensive health check-up in 2015. Participants were asked to respond to a medical interview sheet. We then examined the utility value, as well as lifestyle habits such as alcohol intake, smoking, and exercise. HRQL was examined using EQ-5D-5L. Using a multiple regression analysis, we examined the influence of related factors, such as lifestyle and biochemical test data.Results: We collected 2037 responses (mean age = 54.98 years; 55.0% female). The average preference-based health-related HRQL was 0.936 ± 0.087. A total of 1167 people (57.2%) responded that they were completely healthy. The biochemical test data that were recognized to correlate with HRQL were hemoglobin, total cholesterol, creatinine, all of which were weak (r = - 0.045-0.113). The results of multiple regression analysis showed that significant facts were: being female, age (≧70 year-old), drinking alcohol (sometimes), activity (very often), and lack of sleep.Conclusions: The HRQL of participants who had undergone a comprehensive health check-up was generally high, and only declined for those over 70 years of age. It is suggested that preference-based HRQL is related to physical activity, and that decrease of activity and lack of sleep leads to a decrease in HRQL. [ABSTRACT FROM AUTHOR]