BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated disease with esophageal dysfunction and eosinophil-predominant inflammation. An association between EoE and gastro-esophageal reflux disease (GERD) has not been well established. AIMS: The aim was to evaluate patients with EoE who underwent pH-Multichannel Intraluminal Impedance (pH-MII), investigating proton-pump-inhibitors (PPI) therapy/anti-reflux surgery requirement. METHODS: Twenty-five patients [mean age 7.6 (range 1-17 years)] with EoE underwent pH-MII. The children were then divided into Group 1 (pathological pH-MII) and Group 2 (normal pH-MII). PPI was administered for two months in Group 1 and in those children in Group 2 unresponsive to standard EoE therapy (diet and corticosteroids). All patients underwent endoscopy and clinical follow-up. Data are described as mean (range). RESULTS: Group 1 (n=16, M:F=14:2) had mean reflux index (RI) 13.9% (0.8%-53.4%) with a mean number of total reflux episodes (RE) of 65.8 (14-341). Group 2 (n=9, M:F=6:3) had a mean RI 1.2% (0.2%-2.7%) with a mean number of total RE of 27.4 (14-39). There was a histological response to repeated cycles of PPI in 11/16 (69%) children in Group 1 and 4/9 (44%) children in Group 2. Fundoplication, because of dependence on PPI, was required in 4/11 PPI-responders in Group 1, allowing discontinuation without relapse of EoE. CONCLUSIONS: The use of PPI is suggested in EoE at time of diagnosis in addition to standard treatment and may even have benefit in children who do not appear to have significant GERD but are unresponsive to standard therapy.