BACKGROUND: Patients report that the prophylactic consumption of a proton pump inhibitor minimizes gastrointestinal symptoms expected to be provoked by late-night food and alcohol consumption. The efficacy of this practice has not been studied formally. AIM: To perform a randomized, double-blind, placebo-controlled trial of a single dose of lansoprazole (30 mg) taken prior to a large meal and alcohol consumption. METHODS: Study subjects were recruited randomly from local primary care and hospital physicians. Each participant (n = 56; 37 male, 19 female; mean age, 38 years) completed questionnaires before and after the meal. Approximately 90 min prior to the provocative meal, participants were witnessed taking either placebo or 30 mg lansoprazole. Bar tokens were dispensed to permit the accurate quantification of alcohol consumption (mean, 15 units). RESULTS: Forty per cent of subjects reported significant reflux symptoms. For the entire group, there was no significant difference between lansoprazole and placebo. Post-prandial reflux was more frequent in those consuming > 15 units of alcohol (13/26, 50%) compared with those consuming < 15 units (7/30, 24%; P < 0.05). In the group who consumed > 15 units of alcohol, lansoprazole was associated with a lower rate of heartburn (5/15, 33%) compared with placebo (8/11, 73%; P < 0.05). CONCLUSION: A single dose of a proton pump inhibitor prior to indulgence was only associated with reduced heartburn in those consuming > 15 units of alcohol.