Background/Aims: Growing evidence suggests a negative effect of eosinophilic esophagitis (EoE) on patients’ general health-related quality of life (HRQOL). However, the relevance and use of coping strategies and its relation to (disease specific) HRQOL as well as its determinants have not been studied well. Methods: Adult EoE patients were invited to complete standardized measures on general HRQOL (Short Form-36 Health Survey [SF-36]) and coping strategies (Utrechtse Coping Lijst [UCL]). Scores were compared to general population norms. The disease specific Adult Eosinophilic Esophagitis Quality of Life (EoE-QOL-A) measure was used to assess EoE-HRQOL. Socio-demographic-and clinical factors were also evaluated. Results: In total, 147 adult EoE patients (61% males), age 43 (interquartile range, 29-52) years were analyzed. Mental health-scores (SF-36) were significantly lower in EoE patients, whereas physical health-scores (SF-36) were similar in EoE patients (vs the general population;P = 0.010 and P = 0.240), respectively. The subdomain “disease anxiety” (EoE-QOL-A) was mostly affected, determinants were; female gender, younger age, severe clinical disease activity, higher number of food bolus extraction, and more recent EoE-diagnosis. Less effective coping styles (ie, passive/palliative reaction) were associated with a significant impact on each individual EoE-HRQOLsubdomain as well as lower scores of the Mental Health Component Scale in male EoE patients. Passive reaction in female EoEpatients correlated with impairment of the EoE-HRQOL-domains “emotional impact” and “disease anxiety.” Active problem solving was significantly related to better perception of mental HRQOL (SF-36) in both males and females. Conclusions EoE has a significant negative impact on mental HRQOL, with less effective coping strategies––specifically in males, being a relevant determinant. Thus, a pro-active approach towards coping mechanisms is needed in order to enhance HRQOL and manage patients’ burden of EoE.