Objective: To verify whether cefixime is suitable for the treatment of Helicobacter pylori infection in monotherapy. Design: Prospective, two-centre study with open randomization in two antisecretory treatment schedules. Patients: Duodenal ulcer patients with an endoscopically documented active lesion. Intervention: All patients received antisecretory treatment (either ranitidine 300 mg twice daily or ranitidine 300 mg three times daily) for 31 days (3 weeks+/-10 days) plus cefixime 400 mg four times daily during the fast 10 days. Histology, rapid urease test and culture were used to diagnose H. pylori infection. An upper gastrointestinal endoscopy was performed at the beginning of the study, 31-35 days after starting treatment and 1 month after stopping treatment. Results: Of the 26 patients who joined the study, five were test to follow-up, the ulcer lesion was found unhealed in six out of 21 patients at the end of the therapy and three out of 21 patients were found to be free of H. pylori. One month later, two out of these th ree patients remained free of infection. Ten adverse events were registered, mainly diarrhoea (seven cases). Conclusions: Cefixime is not suitable as monotherapy for H. pylori eradication.