Background: Empirical eradication therapy of H. pylori has been proposed as a therapeutic alternative for duodenal ulcer. Aim: To identify the cost-effectiveness of empirical eradication therapy vs. test-and-treatment for the management of patients already diagnosed with a duodenal ulcer. Methods: A decision analysis was performed to compare the cost-effectiveness of empirical eradication therapy of H. pylori diagnosed duodenal ulcer vs. eradication therapy after confirmatory diagnosis of Helicobacter pylori infection by means of several diagnostic tests. Results: The empirical eradication therapy of duodenal ulcer was found to be the most effective and cost-effective strategy of all the alternatives. Amongst the alternatives, which included the previous performance of confirmatory diagnostic tests, the best cost-effectiveness ratio used a serology test. The model was robust in the face of changes in the values of therapeutic effectiveness, sensitivity and specificity of the diagnostic tests, prevalence of H. pylori infection in duodenal ulcer, duration of the antisecretory therapy, and number of medical visits. Conclusions: Based on our cost-effectiveness analysis, a treat approach is more effective and cost-effective than a test-and-treat approach in the clinical management of already diagnosed duodenal ulcer.