BACKGROUND/AIMS: Long-term maintenance treatment of gastroesophageal reflux disease (GERD) is commonly used to prevent relapse of reflux symptoms; however, due to concerns about safety of long-term proton pump inhibitors (PPI) use, on-demand therapy is recommended as a longterm treatment modality. We compared the efficacy of on-demand and continuous PPI therapy for maintenance treatment of patients with GERD using meta-analysis. METHODS: Core electronic databases were searched for randomized controlled trials comparing on-demand and continuous therapy in GERD patients. The primary outcome was treatment failure of maintenance therapy, and the secondary outcomes included symptomatic relief, patient satisfaction, and amount of PPI use. RESULTS: Overall, 11 studies were selected in the systematic review and meta-analysis. Compared with continuous PPI therapy, on-demand therapy showed similar outcomes for treatment failure (risk ratio, 1.26; 95% confidence interval [CI], 0.76-2.07), particularly in the non-erosive esophageal reflux disease and mild erosive reflux disease group (risk ratio, 1.48; 95% CI, 0.39-5.63). In studies including severe esophagitis patients, continuous PPI maintenance treatment was more effective (β, 0.127 [95% CI, 0.066-0.188]; < 0.001). Severity of esophagitis was associated with higher efficacies of continuous maintenance therapy. The amount of daily PPI use was about half in the on-demand group compared to the continuous group (risk difference -0.52; 95% CI, -0.62--0.42). CONCLUSIONS: On-demand PPI therapy shows comparable efficacy to the continuous maintenance treatment in the non-erosive esophageal reflux disease and mild erosive reflux disease group, and can remarkably reduce the amount of PPI use. Therefore, on-demand therapy may be preferentially recommended in the maintenance treatment of GERD unaccompanied by severe esophagitis.