['The predictors for treatment failure of on-demand proton pump inhibitor (PPI) therapy in gastro-esophageal reflux disease (GERD) patients are unclear. We studied the efficacy and predictors for treatment failure of step-down on-demand PPI therapy in patients with non-erosive reflux disease (NERD) and those with low grade erosive esophagitis.', 'Consecutive symptomatic GERD patients who had positive esophageal pH studies and complete symptom resolution with initial treatment of esomeprazole were given step-down on-demand esomeprazole for 26 weeks. Patients with esophagitis of Los Angeles (LA) grade C or above and recent use of PPI were excluded. Treatment failure was defined as an inadequate relief of reflux symptoms using global symptom assessment. Potential predictors of treatment failure were determined using multivariate analysis.', 'One hundred and sixty three NERD and 102 esophagitis patients were studied. The 26-week probability of treatment failure was 36.2% (95% CI: 23.9-46.5%) in NERD group and 20.1% (95% CI: 10.9-28.3%) in esophagitis group, respectively (P = 0.021). Irritable bowel syndrome (adjusted HR: 2.1, 95% CI: 1.5-3.8, P = 0.01), in addition to daily reflux symptom (adjusted hazard ratio: 2.7, 95% CI: 1.9-4.2, P = 0.001) and concomitant dyspepsia (adjusted hazard ratio: 1.7, 95% CI: 1.1-2.8, P = 0.04), were independent predictors for treatment failure.'] Is concomitant irritable bowel syndrome associated with failure of step-down on-demand proton pump inhibitor treatment in patients with gastro-esophageal reflux disease?