Objective A holistic and comprehensive analysis of traditional Chinese medicine (TCM) constitutions health states was conducted to explore the impact of different concurrently clamped constitution histories on health-related quality of life (HRQOL). Methods Using the convenient sampling method, the Constitution in Chinese Medicine Questionnaire-41 entry short version, the Chinese verison of SF- 36, and other tools were used to measure the unpaid blood donor population aged 18 to 60 years old, and the fuzzy set qualitative comparative analysis was used to explore configuration of the TCM constitution that affected HRQOL. Results The mean age of the 2 254 study subjects included in the analysis was (30. 72±9. 78) years. The percentage of gentleness constitution was 35. 71%, and 33. 81% had a combination of more than 3 types biased constitutions. Three categories of TCM constitution groupings negatively influenced HRQOL in the physiological domain. First, non-gentleness constitution, qi-deficiency constitution, yang-deficiency constitution, phlegm-wetness constitution, and blood-stasis constitution were the core conditions; second, non-gentleness constitution, qi-deficiency constitution, phlegm-wetness constitution, blood-stasis constitution and special diathesis constitution were the core conditions; and third, all eight biased constitutions were present as core conditions. Three categories of TCM constitution groupings negatively influenced HRQOL in the psychological domain. First, non-gentleness constitution, qideficiency constitution, phlegm-wetness constitution, blood-stasis constitution, and qi-depression constitution were the core conditions; second, non-gentleness constitution, qi-deficiency constitution, yin-deficiency constitution, wetness-heat constitution, and qi-depression constitution were the core conditions; and third, all eight biased constitutions occurred as core conditions. Conclusion The fuzzyset qualitative comparative analysis method with a configuration perspective revealed the effect of TCM constitution on HRQOL as a multi-component combination of concurrent mechanisms. The diversity of concurrently clamped constitution and the complexity of its relationship with HRQOL were fully analyzed, and this results provide a reference direction for researchers to dig deeper into the intervention pathways of TCM constitution conditioning to enhance quality of life. [ABSTRACT FROM AUTHOR]