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Background and Aims: It is difficult to differentiate functional heartburn from proton pump inhibitor (PPI) failure. The aims of this study were to assess the role of early wireless esophageal pH monitoring in patients referred with gastroesophageal reflux disease (GERD) and to identify differences in the clinical spectrum among GERD subtypes. Methods: We enrolled consecutive referred patients with suspected GERD. After endoscopy on the first visit, all underwent wireless esophageal pH monitoring when off the PPI. Results: Two hundred thirty patients were enrolled. These patients were classified into a reflux esophagitis group (20, 8.7 %) and a normal endoscopic findings group (210, 91.3 %). Among the 210 patients in the normal endoscopic findings group, 63 (27.4 %) were diagnosed with pathological reflux, 35 (15.2 %) with hypersensitive esophagus, 87 (37.8 %) with normal acid exposure with negative symptom association, and 25 (10.9 %) with test failure. These groups did not differ in age, body mass index, smoking habit, alcohol consumption, symptom severity, quality of life, presence of atypical symptoms, overlap with irritable bowel syndrome, and the frequency of somatization, depression, and anxiety. PPI responses were evaluated in 135 patients. Fifty patients (37.0 %) were not responsive to the 4-week treatment; 26 (19.3 %) were diagnosed with refractory non-erosive gastroesophageal disease, and 24 (17.8 %) with functional heartburn. The demographics and clinical and psychological characteristics did not differ between the two groups. Conclusions: Demographic characteristics and symptom patterns alone cannot differentiate functional heartburn from various subtypes of GERD. Wireless esophageal pH monitoring should be considered for the initial evaluation of GERD in the tertiary referral setting. [ABSTRACT FROM AUTHOR]