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Abstract: Background and study aims: Helicobacter pylori is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. In the past two decades, the recommended treatment for its eradication as a first-line regimen is the standard triple therapy consisting of a proton pump inhibitor (PPI), amoxicillin and clarithromycin or metronidazole. However, the effectiveness of this traditional regime, which initially was 90%, progressively declined in many parts of the world and is currently 57–73%. The aim of this study was to evaluate whether the eradication rate with triple therapy with levofloxacin is superior as first-line therapy to that with treatment using clarithromycin in the population that attended as outpatients at the Hospital of Lídice. Patients and methods: We designed a prospective study, with two groups of patients presenting dyspeptic symptoms, from October 2010 to October 2011, who underwent upper gastrointestinal endoscopy and whose biopsies were positive for infection with H. pylori. At the end, 81 patients were included in the order of biopsy result arrival to fill the quota of each group. The first group with 42 patients underwent triple therapy with clarithromycin and the second group with 39 patients underwent therapy with levofloxacin, amoxicillin and a PPI. The patients’ age ranged between 23 and 76years, the average being 49.5. The predominant sex was female, at 72.84%. Both treatments lasted for 10days and the patients were clinically re-evaluated 15days after their conclusion and programmed for a second endoscopy to verify H. pylori eradication. Results: Among the 42 patients in the control group, there were 14 eradication failures with 33.33% resistance to clarithromycin. Among the 39 patients in the experimental group, two eradication failures with 5.13% resistance to levofloxacin were observed. The χ 2 value was 6.96. Conclusions: Treatment with levofloxacin was more effective than conventional triple therapy. Triple therapy with levofloxacin can be implemented in populations where resistance to clarithromycin has been observed. [Copyright &y& Elsevier]