Approximately half of patients with eosinophilic esophagitis (EoE) respond clinically and histologically to proton pump inhibitor (PPI) therapy. Although recent guidelines suggest that PPI-responders and non-responders were included in EoE, it is important to investigate the predictive factors of PPI- responsiveness. This study aimed to determine the rate of PPI- responders and compare the characteristics of PPI-responders and non-responders. Fifty-nine patients with esophageal eosinophilia received PPI therapy for eight weeks, and its efficacy was assessed. PPI- responsiveness was diagnosed based on the relief in symptoms and reduction of intraepithelial eosinophilic infiltration to <15 per high-power field (hpf) after PPI therapy. Multivariate analysis was performed to identify factors associated with PPI-responders. Of the 59 patients, 41 (69.5%) were diagnosed with PPI-responders. The rate of gastrointestinal (GI) screening in the indications for endoscopy was significantly higher in patients with PPI- responders than in those with non-responders. On multivariate analysis, GI screening and presence of reflux esophagitis was associated with an increased odds ratio (OR) of PPI-responders, but presence of rings with a decreased OR of PPI-responders. Presence of reflux esophagitis and absence of rings on endoscopy especially during GI screening might be significant predictive factors for PPI response in patients with EoE.