Background: Helicobacter pylori is the main causative agent in peptic ulcer disease. Duodenal ulcer disease is a chronic, recurring condition, and the risk of recurrence and complications does not diminish over time unless H pylori is eradicated. Several treatment protocols exist to eradicate H pylori, but their efficacy and costs vary. Because of regional variations in bacterial resistance and in treatment costs, primary care physicians must use the most appropriate protocol for their own region and population. Objective: The primary aim of this study was to compare the cure rates obtained with 5 different H pylori eradication protocols in H pylori—positive duodenal ulcer patients in Turkey. A secondary objective was to determine the accuracy of the duodenal ulcer diagnoses made by primary care physicans relying on information from physical examination and medical history alone. Methods: In a primary care setting, 2 family physicians, 5 general physicians (medical school graduates), 1 general surgeon, and 1 internal medicine specialist identified 265 symptomatic duodenal ulcer patients using medical history and physical examination results. These patients were referred to an open-access endoscopy unit for upper gastrointestinal endoscopy. Patients who had an endoscopically confirmed duodenal ulcer and who tested positive for H pylori were randomly assigned to receive 1 of 5 H pylori eradication treatments: (1) omeprazole/amoxicillin/clarithromycin; (2) lansoprazole/amoxicillin/clarithromycin; (3) omeprazole/ornidazole/amoxicillin; (4) lansoprazole/amoxicillin/clarithromycin/ornidazole, or (5) ranitidine bismuth citrate/amoxicillin/metronidazole. Follow-up endoscopies and biopsies were performed 6 weeks and 6 months after the end of treatment. Results: Of the 265 patients suspected to have duodenal ulcers based on medical history and physical examination findings, 181 (68.3%) had endoscopically confirmed duodenal ulcers. At both 6 weeks and 6 months after treatment, eradication rate were not significantly different between treatment groups in the intent-to-treat or per-protocol analyses. There was no significant difference in tolerability between the 5 regimens. Conclusions: Our results confirm the high accuracy of the duodenal ulcer diagnoses and endoscopy referrals made by primary care physicians based on physical examination and medical history of the patient. Primary care physicians should play an important role in treatment decisions regarding H pylori eradication. The 5 treatments studied are similar with respect to H pylori eradication rates. If the cost of treatment is an important consideration, the less expensive omeprazole/ornidazole/amoxicillin triple regimen may be a good choice for eradicating H pylori. In cases of resistant H pylori infection, the lansoprazole/amoxicillin/clarithromycin/ornidazole quadruple therapy appears to be the best choice for a second-line treatment if reliable culture and resistance testing are not available. Depending on regional variables, each nation needs to develop its own guidelines for the eradication of H pylori.