AIM To determine the impact of upwards titration of proton pump inhibition(PPI) on acid reflux, symptom scores and histology, compared to clinically successful fundoplication.METHODS Two cohorts of long-segment Barrett’s esophagus(BE) patients were studied. In group 1(n = 24), increasing doses of PPI were administered in 8-wk intervals until acid reflux normalization. At each assessment, ambulatory 24 h p H recording, endoscopy with biopsies and symptom scoring(by a gastroesophageal reflux disease health related quality of life questionnaire, GERD/HRLQ) were performed. Group 2(n = 30) consisted of patients with a previous fundoplication. RESULTS In group 1, acid reflux normalized in 23 of 24 patients, resulting in improved GERD/HRQL scores(P = 0.001), which were most pronounced after the starting dose of PPI(P < 0.001). PPI treatment reached the same level of GERD/HRQL scores as after a clinically successful fundoplication(P = 0.5). Normalization of acid reflux in both groups was associated with reduction in papillary length, basal cell layer thickness, intercellular space dilatation, and acute and chronic inflammation of squamous epithelium. CONCLUSION This study shows that acid reflux and symptom scores co-vary throughout PPI increments in long-segment BE patients, especially after the first dose of PPI, reaching the same level as after a successful fundoplication. Minor changes were found among GERD markers at the morphological level. AIM To determine the impact of upwards titration of proton pump inhibition (PPI) on acid reflux, symptom scores and histology, compared to clinically successful fundoplication. METHODS Two cohorts of long-segment Barrett’s esophagus (BE) patients were studied. In group 1 ( At each assessment, ambulatory 24 hp H recording, endoscopy with biopsies and symptom scoring (by a gastroesophageal reflux disease health related quality of life questionnaire, n = 24), increasing doses of PPI were administered in 8-wk intervals until acid reflux normalization. RESULTS In group 1, acid reflux normalized in 23 of 24 patients, resulting in improved GERD / HRQL scores (P = 0.001), which group GERD / HRLQ PPI treatment reached the same level of GERD / HRQL scores as after a clinically successful fundoplication (P = 0.5). Normalization of acid reflux in both groups was assoc iated with reduction in papillary length, basal cell layer thickness, intercellular space dilatation, and acute and chronic inflammation of squamous epithelium. CONCLUSION This study shows that acid reflux and symptom scores co-vary throughout PPI increments in long-segment BE patients, especially after the first dose of PPI, reaching the same level as after a successful fundoplication. Minor changes were found among GERD markers at the morphological level.