Background : Many dual and triple therapy treatment regimens have been proposed for the eradication of Helicobacter pylori. However, assessing the relative efficacy of these regimens is complicated by differences in study design, and few well‐controlled comparative studies have been reported. Methods : This multicentre, randomized, double‐blind study involved 530 duodenal ulcer patients, of whom 520 had confirmed H. pylori infection. Patients received 14 days b.d. dual therapy of either ranitidine bismuth citrate (RBC) 400 mg or omeprazole 20 mg, both with clarithromycin 500 mg to eradicate H. pylori, followed by a further 14 days of treatment with RBC 400 mg b.d. or omeprazole 20 mg o.d. to facilitate ulcer healing. H. pylori eradication and ulcer healing were assessed at least 26 days after the end of treatment. Adverse events were recorded throughout the study. Results : H. pylori was eradicated in 90% of patients who received RBC with clarithromycin and in 66% of patients who received omeprazole with clarithromycin (per protocol; P < 0.001). intention‐to‐treat eradication rates were 77% and 60%, respectively (P < 0.001). Ulcer healing rates were 97% in the RBC treatment group and 95% in the omeprazole treatment group. Only 3% and 1% of patients in the RBC and omeprazole treatment groups, respectively, were withdrawn due to adverse events. Conclusions : RBC with clarithromycin is a simple and highly effective dual therapy regimen for the eradication of H. pylori, and is significantly more effective than omeprazole with clarithromycin. Both treatment regimens are well tolerated and effectively heal duodenal ulcers.