ABSTRACT: BACKGROUND/AIMS:Proton pump inhibitors (PPIs) are widely used in the treatment of gastroesophageal reflux disease (GERD). However, some patients fail to respond to PPI therapy. We investigated the efficacy of response to PPI therapy in patients with GERD symptoms. METHODS:A total of 179 subjects with GERD symptoms were prospectively enrolled and diagnosed with non-erosive reflux disease (NERD, n = 100) and erosive reflux disease (n = 79) by gastroscopy and Bernstein test and/or 24-hour esophageal pH testing. Subjects then received a standard dose of daily PPI therapy for at least 4 weeks. PPI therapy response was evaluated using questionnaires including questions about demographics, GERD symptoms, GERD impact scale, Epworth sleepiness scale, Pittsburgh sleep quality index (PSQI), hospital anxiety and depression scale, and abbreviated version of the World Health Organization quality of life scale. RESULTS:The rates of complete (? 80%), satisfactory (? 50%), partial (< 50%), and refractory response in the 179 participants were 41.3%, 30.2%, 18.4%, and 10.1%, respectively. Thus, overall response rate (complete and satisfactory responses) was 71.5%. Multivariate analysis showed body mass index < 23 kg/m(2) (OR, 2.20; 95% CI, 1.12-4.34), higher total PSQI score (OR, 1.20; 95% CI, 1.05-1.35), history of psychotherapy or neuropsychiatric medication (OR, 2.44; 95% CI, 1.23-4.85), and NERD (OR, 3.30; 95% CI, 1.54-7.11) were associated with poor response to PPI therapy. CONCLUSIONS:Psychological factors, sleep dysfunction, body mass index < 23 kg/m(2), and NERD seem to be the major factors that lead to a poor response to PPI treatment in patients with GERD symptoms.