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Objectives: To study the health-related quality of life (HRQoL) and its possible determinant factors in Spanish children with eosinophilic esophagitis (EoE) and their parents., Methods: Multicenter observational cross-sectional study. The Spanish version of the Pediatric Quality of Life Eosinophilic Esophagitis Module was filled out by EoE patients aged 8-18 and their parents. Demographic, psychosocial, and clinical variables were studied. Multiple linear regression was performed to identify related factors of HRQoL., Results: A total of 279 children and their parents participated (72.7% males). 39.1% received swallowed corticosteroids, 35.5% proton pump inhibitors and 16.8% diet. 1.1% received other treatments and 7.5% received no treatment. Poor compliance to treatment was observed in 11.5% and 6.5% of patients were referred to mental health. The Total Scale Scores were 72.71 ± 17.50 and 75.62 ± 16.73 for children and parents, respectively. "Communication" was the dimension with the highest scores (82.14 ± 21.65 and 81.59 ± 24.13) while "Food and Eating" (48.92 ± 32.94 and 62.85 ± 28.78), and "Food Feelings" (53.55 ± 29.96 and 53.95 ± 27.78) had the lower scores. Patients and parents under dietary treatment showed lower scores than those under pharmacological treatment, 65.77 ± 16.96 versus 74.28 ± 16.96, p = 0.001 and 68.33 ± 17.32 versus 77.24 ± 15.97, p = 0.001, respectively. Factors associated with worse HRQoL scores were symptom frequency, diet, food allergies, and the need for mental health assistance., Conclusions: The HRQoL of children and their parents was "good." However, diet, frequency of symptoms, food allergies, and the need for mental health care were the factors that had a negative impact on HRQoL of children with EoE., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)