Background and aim: Helicobacter pylori (H. pylori) infection can cause chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. For this reason, eradication of H. pylori has become an important issue. In recent years, failure of eradication therapy with standard eradication regimes had directed toward new therapeutic alternatives. The present study aimed to show the efficacy of bismuth-containing quadruple regimen for the first-line treatment of H. pylori infection. Materials and methods: H. pylori positive patients received a quadruple therapy consisted of esomeprazole 20 mg bid, colloidal bismuth subcitrate 600 mg bid, tetracycline 500 mg qid and metronidazole 500 mg tid for 7 days. The diagnosis of H. pylori infection was performed by the histopathological assessment of gastric biopsies. Six weeks after completion of therapy, H. pylori status was rechecked by C14 urea-breath test. Results: A total of 115 patients have completed the protocols (upper gastrointestinal endoscopy, treatment, urea-breath test). H. pylori eradication rate was found to be 87%. This eradication rate is significantly higher than those of classic triple therapies in the literature. Conclusion: The bismuth-containing quadruple regimen achieved an acceptable and very higher eradication rate than those of classic triple therapies in the literature. It can recommend as a first-line therapy for Helicobacter pylori infection.