Patients with Eosinophilic esophagitis (EoE) require long-lasting resolution of inflammation to prevent fibrostenosis and dysphagia. However, the dissociation between symptoms and histologic improvement suggests persistent molecular drivers despite remission. We aimed to characterize persisting molecular alterations in pediatric patients with EoE using tissue proteomics. Esophageal tissue biopsies (n=151) and clinical data were collected prospectively from pediatric patients with EoE (N=34), gastroesophageal reflux disease (GERD; N=10; inflammatory controls) or functional disorders (FD; N=20; non-inflammatory controls). Biospies (n=131) acquired from the diagnostic endoscopy and up to 7 follow-ups were considered for proteome analysis in patients with EoE, while for GERD and FD only biopsies from initial diagnosis were included. Histologically active EoE (15 eosinophils per high power field (hpf)) was diagnosed in 79 biopsies and 52 samples derived from patients with EoE in remission (15 eosinophils per hpf). After microdissection of the epithelium proteins were extracted from the esophageal tissue followed by a liquid chromatography-tandem mass spectrometry. Proteomic analysis identified 3,704 different proteins in total across all samples.