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Background: There is no current and broad consensus about the eradication of Helicobacter pylori (HP) infection in gastric ulcer and indigestion diseases. Objective: This study aimed to compare three regimens based on clarithromycin, furazolidone, and levofloxacin in patients with HP infection. Materials and Methods: This study was a randomized clinical trial examining 102 patients with gastrointestinal diseases. They were randomly assigned to three equal groups. In the first group, basic medication (i.e., a combination of esomeprazole 40 mg and amoxicillin 1000 mg) with clarithromycin 1000 mg was prescribed. The second group was treated with basic medication regimen along with furazolidone 400 mg. And the third group was given the basic medication with levofloxacin 500 mg. Eradication rates of the HP infection and incidence rates of drug side-effects in the three groups were compared after two-week and the obtained data were analyzed using appropriate statistical methods. Results: According to our study results, the HP infection eradication rates revealed by the per-protocol (PP) and intention-to-treat (ITT) analyses for the levofloxacin group were 91.2% and 93.8%, respectively, which were significantly different from those found for the furazolidone group by PP analysis and for the clarithromycin group by PP and ITT analyses (P<0.05). Moreover, there were no significant differences among the three groups regarding the side effects (P>0.05). Conclusion: It was concluded that two-week regimen of levofloxacin together with a single-dose of esomeprazole and amoxicillin was desirable (90%-95%) and more effective than furazolidone and clarithromycin in eradicating HP.