OBJECTIVES: Patients with acid-related symptoms in general practice are often treated empirically with a standard dose of proton pump inhibitors (PPIs). The effect of higher doses is not known. The study compared the immediate symptom relieving as well as the long-term effect of standard and double dose of omeprazole in such patients. METHODS: Consecutive patients with dyspeptic symptoms, normally treated by the general practitioner with PPIs or H2-blockers were randomized to treatment with omeprazole 40 mg, 20 mg, or placebo in the morning for 2 wk. Patients with alarm symptoms, IBS, and PPI-treated patients were excluded. Dyspeptic symptoms and Helicobacter pylori status were recorded. The study endpoint was complete relief of the dyspeptic symptoms, which initiated the consultation. Relapse rates and health-care consumption were recorded during 12-month observation. RESULTS: Eight hundred and twenty-nine patients were randomized. Complete relief of the predominant symptom was obtained by 66%, 63%, and 35% in patients treated with omeprazole 40 mg, 20 mg, and placebo, respectively. No difference was found comparing H. pylori-positive and -negative patients. Relapse rates were high and health-care consumption during 12 months was related to the treatment outcome, but not to the omeprazole dose or the H. pylori status. CONCLUSIONS: Compared to placebo, omeprazole 40 mg and 20 mg were equally and significantly better in relieving acid-related symptoms; the numbers needed-to-treat (NNT) were 3.2 (40 mg) and 3.7 (20 mg). Relief of the dyspeptic complaint was followed by significantly reduced health-care consumption during 12-month observation.