BACKGROUND: The use of vitamin C as a supplement with the common regimen for eradication of Helicobacter pylori infection is the subject of ongoing controversy. We conducted a prospective controlled study with the aim of testing whether the vitamin C supplement to the therapy includes lower dosage of clarithromycin could have an acceptable influence on Helicobacter pylori eradication in comparison with routine anti-Helicobacter pylori regimen. MATERIALS AND METHODS: Two hundred and fourteen consecutive patients with the verification of Helicobacter pylori infection via positive Rapid Urease Test (RUT) and histology results were included and divided into two therapy groups: 1) a group without vitamin C (n = 100) that were administered 20 mg omeprazol, 1 g amoxicillin, and 500 mg clarithromycin twice daily for 2 weeks and 2) a triple-plus-vitamin C group (n = 114) that was administered 20 mg omeprazol, 1 g amoxicillin, 250 mg clarithromycin plus 250 mg vitamin C twice daily for 2 weeks. Four weeks after the completion of therapy, each patient was scheduled for urea breath test to assess the success of Helicobacter pylori eradication. RESULTS: Similar eradication of Helicobacter pylori was found between the triple-only group with 500 mg of clarithromycin and the triple with 250 mg of clarithromycin-plus vitamin C group (89% versus 86.8%, P = 0.623). CONCLUSIONS: Adding vitamin C might reduce the needed dosage of clarithromycin for eradication of Helicobacter pylori.