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Objective To evaluate the eradication rates, side effects and the patient compliance of a dual therapy with rabeprazole and amoxicillin as the first-line therapy in patients with Helicobacter pylori (H. pylori) infection. Methods A total of 120 patients diagnosed endoscopically with non-ulcer dyspepsia with H. pylori infection were randomly assigned into two groups, one treated with amoxicillin 1 g thrice daily plus rabeprazole 10 mg twice daily ( R10 A group) or 20 mg twice daily ( R20 A group) for 14 days. H. pylori eradication was evaluated by 13 C-urea breath test ( UBT) at 4-6 weeks after the completion of treatment. H. pylori eradication rate was analyzed by per-protocol ( PP) and intention-to-treat ( ITT) analyses together with 95% confidence interval ( CI). Side effects and patients' compliance were also recorded. Results Overall, 117 patients (58 in the R10 A group and 59 in the R20 A group) completed the study, among whom five did not undertake the UBT. H. pylori eradication was achieved in 89.8% of patients in the R20 A group by ITT analysis and 93.0% by PP analysis, which was significantly higher than those in the R10 A group (75.9% and 80.0%, respectively, P < 0.05). Side effects, including skin rash, abdominal discomfort, headache, insomnia and nausea, were all mild and were treated symptomatically without the need to discontinue the treatment. Conclusion The modified dual therapy with high doses of rabeprazole and amoxicillin is considered an effective and safe primary therapy for H. pylori eradication and could be recommended as the first-line eradication regimen for certain patients. [ABSTRACT FROM AUTHOR]