Background: Helicobacter pylori is the main pathogenic factor for chronic gastritis and peptic ulcer disease. Therefore, its successful eradication is important in the disease management. Multiple first-line treatments have been employed; the eradication rates in the most successful regimens have been 75%-92%. Primary bacterial resistance to antibiotics and patient compliance are two main cause of therapy failure. Furazolidone with a broad spectrum of antimicrobial activities is widely used in the treatment of bacterial and protozoal infections in both humans and animals, which could also be used in treatment of H. pylori infection. Objectives: This study was designed to evaluate the efficacy of the therapeutic regimen containing furazolidone in comparison with a standard regimen against H. pylori. Materials and Methods: In this randomized clinical trial, 110 patients with a positive urease breath test (UBT) were selected and randomly divided into two equal groups. The first group received the standard regimen consisting of clarithromycin (500 mg Q12h), amoxicillin (1 g Q12) and a proton pump inhibitor (PPI) (omeprazole 20 mg BID). The second group received bismuth subcitrate (120 mg Q6h), furazolidone (100 mg Q6h) and tetracycline (250 mg Q6h) and a PPI (omeprazole 20 mg BID) for two weeks. UBT was performed again for all the patients two months after completing. Results: UBT was negative in 83.6% of patients in the standard group two months after the end of the treatment. Eradication of H. pylori was reported in 94.5% of patients in the experimental group. No significant relationship between age and eradication of H. pylori was observed in both groups. Nausea and vomiting was reported in 5.45% of patients treated with our experimental regimen. These symptoms were tolerable and the treatment was completely continued. No adverse effect was recorded in the standard group. Moreover, no relationship was observed between gender and eradication of H. pylori in both groups. Finally, despite a better therapeutic response to our experimental group in comparison with the standard one, no statistically significant difference was observed (P = 0.067). Conclusions: Based on our finding in this study and similar studies in different parts of the world, furazolidone could be prescribed as an effective antibiotic against H. pylori in patients with gastritis.