BACKGROUND Optimal long-term management of symptomatic gastro-oesophageal reflux disease (sGERD) patients has not been established. OBJECTIVE To determine the clinical value of maintenance intermittent treatment with rabeprazole 20 mg vs. placebo in patients with sGERD. METHODS This multicentre, US study enrolled patients with sGERD (>or=3-month history of GERD symptoms and >or=4 days/week of heartburn during a 2-week placebo run-in) without oesophageal erosions. Patients with complete heartburn control after 4 weeks of open-label rabeprazole 20 mg daily treatment were randomized to 6-month, double-blind, maintenance intermittent treatment (7- to 14-day courses when heartburn recurred) with rabeprazole 20 mg or placebo. RESULTS The primary efficacy end point, mean percentage of heartburn-free days, was significantly greater with rabeprazole vs. placebo: 82.58% and 62.17% (ITT; P < 0.0001) [per protocol 86.74% rabeprazole vs. 74.93% placebo (P < 0.0254)]. Compared with placebo group, the rabeprazole group also experienced a significantly higher percentage of heartburn-free daytime (84.06% vs. 63.39%; P < 0.0001) and nighttime (95.41% vs. 90.25%; P = 0.0021) periods, had significantly fewer discontinuations because of insufficient heartburn control (6.3% vs. 36.3%; P < 0.0001) and took fewer antacid tablets daily (0.58 vs. 1.16; P = 0.0021). CONCLUSIONS Intermittent use of rabeprazole may be an effective maintenance treatment strategy for patients with sGERD and warrants further investigation. This trial was registered with http://clinicaltrials.gov under the number NCT00165841.