Background/aims: Proton-pump inhibitor- and ranitidine bismuth citrate-based triple regimens are the two recommended first- line treatments for the eradication of Helicobacter pylori. We aimed to compare the effectiveness and tolerability of these two treat- ments in a prospective, multi-centric, randomized study. Materials and Methods: Patients with dyspeptic complaints were recrui- ted from 15 study centers. Presence of Helicobacter pylori was investigated by both histology and rapid urease test. The patients we- re randomized to either ranitidine bismuth citrate 400 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=149) or lansoprazole 30 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=130) treatment arm for 14 days. Adverse events have been recorded during the treatment phase. A 13C urea breath test was performed 6 weeks after termination of treatment to as- sess the efficacy of the therapy. Eradication rate was calculated by intention-to-treat and per-protocol analysis. Results: Two hun- dred seventy-nine patients (123 male, 156 female) were eligible for randomization. In per-protocol analysis (n=247), Helicobacter pylori was eradicated with ranitidine bismuth citrate- and lansoprazole-based regimens in 74,6% and 69,2% of cases, respectively (p>0,05). Intention-to-treat analysis (n=279) revealed that eradication rates were 65,1% and 63,6% in ranitidine bismuth citrate- and in lansoprazole-based regimens, respectively (p>0,05). Both regimes were well-tolerated, and no serious adverse event was ob- served during the study. Conclusion: Ranitidine bismuth citrate-based regimen is at least as effective and tolerable as the classi- cal proton-pump inhibitor-based regimen, but none of the therapies could achieve the recommendable eradication rate.