(1) Background: In Vietnam, H. pylori bacteria has a resistance rate of 63% to the antibiotic clarithromycin. The initial therapy of H. pylori eradication with a standard three-drug regimen has low efficacy. Objective: Assess the efficacy of H. pylori eradication therapy which uses a four-drug regimen of rabeprazole–bismuth–tetracycline–tinidazole in patients with duodenal ulcers. (2) Methods: We performed gastrointestinal endoscopy on patients with a diagnosis of duodenal ulcers, gastric mucosa biopsy for a rapid urease test, and histopathology to diagnose H. pylori bacteria before and after treatment. Treatment for eradication of H. pylori bacteria using a rabeprazole–bismuth–tetracycline–tinidazole regimen was prescribed for 14 days. (3) Results: The rate of successful H. pylori eradication treatment according to per protocol (PP) and intention to treat (ITT) was 91.3% (95%CI: 84.8–96.7) and 82.4% (95%CI: 74.5–89.2) respectively. The success rate of H. pylori eradication therapy in males was 96.0% (95%CI: 92–100), higher than in females, which was 70.6% (95%CI: 47.1–88.2), pH. pylori with rabeprazole–bismuth–tetracycline–tinidazole regimen is highly effective. Men had higher H. pylori eradication results than women. View Full-Text ►▼ Show Figures This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.