While night-time symptoms of gastroesophageal reflux disease (GERD) are common, considerable controversy exists regarding the use of histamine-2 receptor antagonists (H2Ras) for night-time reflux control. Some studies have suggested possible tolerance to H2RA while others have suggested that long-term efficacy of gastric acid control can be maintained with night-time H2RA use. The aim of this study was to identify if GERD patients have sustained symptom improvement with long-term use of night-time H2RA. Records of 56 consecutive GERD patients on twice daily proton pump inhibitor (PPI) and night-time H2RA therapy were reviewed. During a phone interview patients were asked a 5-item questionnaire, which included overall assessment of symptoms, night-time symptoms, sleep disturbance, duration and frequency of therapy. Of the 56 patients, 39 (31 women, mean age 56) completed the questionnaire (15 were not reached and 2 did not recall enough information). All respondents had taken night-time H2RA for at least 1 month (28/39 patients with > 6 months duration) with 33/39 patients taking H2RAs every night. The addition of H2RA led to an improvement in overall symptoms in 28/39 (72%) patients, improvement in night-time reflux symptoms in 25/34 (74%) patients and improvement of GERD-associated sleep disturbance in 18/27 (67%) patients. Five (13%) patients had stopped the H2RA on their own, stating that its efficacy waned after 1 month. Our results suggest that the majority of patients report persistent improvement in GERD symptoms from night-time H2RA use and that possible clinically important tolerance to H2RAs occurs in a small number of patients. Further prospective, placebo-controlled studies may help confirm that there is a role for night-time H2RAs in GERD symptom control.