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Background Health-related quality of life (HRQOL) is increasingly measured as an outcome for clinical and health services research. However, relatively little is known about how non-health factors affect HRQOL. Personality is a potentially important factor, yet evidence regarding the effects of personality on HRQOL measures is unclear. Methods This systematic review examined the relationships among aspects of personality and HRQOL. Eligible studies were identified from Medline and PsycINFO. The review included 76 English-language studies with HRQOL as a primary outcome and that assessed personality from the psychological perspective. Individuals with various health states, including ill (e.g., cancer, cardiovascular disorders), aging, and healthy, were included in this review study. Results Some personality characteristics were consistently related to psychosocial aspects more often than physical aspects of HRQOL. Personality characteristics, especially neuroticism, mastery, optimism, and sense of coherence were most likely to be associated with psychosocial HRQOL. Personality explained varying proportions of variance in different domains of HRQOL. The range of variance explained in psychosocial HRQOL was 0 to 45% and the range of explained variance in physical HRQOL was 0 to 39%. Conclusions Personality characteristics are related to HRQOL. Systematic collection and analysis of personality data alongside HRQOL measures may be helpful in medical research, clinical practice, and health policy evaluation.

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