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Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease characterized by esophageal inflammation and dysfunction. Little is known about the humanistic and economic burden of the disease on patients, their caregivers, and the health care system. A systematic review was conducted to evaluate the existing literature on the disease burden of EoE for patients and their caregivers.The MEDLINE, Embase, and Evidence-Based Medicine Reviews databases and recent congresses were searched on March 23, 2017, for English-language publications describing the impact of EoE on health-related quality of life (HRQoL) in children and adults, and the economic burden associated with the disease.Of 676 articles identified, 22 met the inclusion criteria and were included in this analysis (HRQoL, 13; economic burden, 7; cost effectiveness, 2). The included studies showed that EoE is associated with a significant impact on HRQoL, resulting in disruption to and restrictions on daily life for patients, their caregivers, and, in some instances, their families. Treatment with topical corticosteroids, the 6-food elimination diet, or the cow’s milk elimination diet significantly improved the HRQoL of patients with EoE. Symptom severity was associated strongly with the impact of EoE on HRQoL. Medical resource utilization costs for patients with EoE were significantly higher than those for healthy controls.EoE negatively impacts the HRQoL of patients and their families, and is a burden to the health care system. Although data are sparse, currently available treatments appear to improve HRQoL.