SUMMARY Background: Helicobacter pylori eradication with omeprazole and clarithromycin varies between 40 and 80%. The dose, frequency and duration of treatment may account for these differences. Lansoprazole, a recently introduced proton pump inhibitor, is a more potent H. pylori bacteriostat in vitro than omeprazole. The aim of this open, comparative, randomized study was to investigate the efficacy and safety of lansoprazole 30 mg once or twice a day (and for 2 vs. 4 weeks) plus clarithromycin 500 mg t.d.s. for 2 weeks, in the eradication of H. pylori. Methods: Sixty‐six patients with H. pylori infection received clarithromycin 500 mg t.d.s. for 2 weeks and one of four lansoprazole regimens: 30 mg once a day for 2 (Group 1, n= 16) or 4 (Group 2, n= 16) weeks, or 30 mg b.d. for 2 (Group 3, n= 18) or 4 (Group 4, n= 16) weeks. H. pylori eradication was determined by the 13C‐urea breath test 4 weeks after finishing treatment. Results: Per protocol analysis (53 patients) shows that H. pylori was eradicated in 6/13 (46%) in Group 1, 7/13 (54%) in Group 2, 9/14 (64%) in Group 3 and 9/13 (69%) in Group 4. Thirty‐one of 68 patients experienced side effects. Analysis on an intention‐totreat basis gave similar results. Conclusion: The dose of lansoprazole appears to be more important than the duration of therapy. Dual therapy with lansoprazole and clarithromycin should be investigated further as a possible treatment regimen for H. pylori infection.