Background and study aims: to evaluate efficacy of Furazolidone versus clarithromycin in quadruple therapy for eradication of Helicobacter Pylori (HP) infection . Patients and Method: During a period of six months, all of the cases with HP infection in 3 referral tertiary centers included. The participants randomly allocate to receive either clarithromycin or Furazolidone base quadruple regimen. For all of the participants pantoprazole continued for 4 more weeks and after 1 to 2 weeks of off therapy, they underwent Urea Breath Test to prove eradication. Results: Overall 386 patients included (165 male (42%), average age 44.2y). They diagnosed as non-ulcer dyspepsia (311 cases), peptic ulcer disease (34 cases) and intestinal metaplasia (45 cases). The participants randomly allocated to groups A & B to receive either clarithromycin or Furazolidone. In groups A and B, 80.9% & 82.1% of participants achieved eradication respectively (P = 0.819). During study, there was not any major complication but 3.1% of participants in each group reported minor side effects including bitter taste, Gastrointestinal (GI) upset, headache and or vertigo. In sub group analysis, the eradication rate of clarithromycin among patients with non-ulcer dyspepsia, peptic ulcer disease (PUD) and intestinal metaplasia were 80%, 100% & 55.6% respectively. These figures in group B (Furazolidone) were 80.7%, 100% & 85.7% respectively (P= 0.906, 0 & 0.162). Overall, there was no significant difference in success rate between clarithromycin and Furazolidone but in cases with intestinal metaplasia, the positive results with Furazolidone was more (85.7% vs. 55.6%). Conclusion: In areas with high rate of resistance to clarithromycin, Furazolidone could be a potential candidate in HP eradication regimen and in cases with intestinal metaplasia; Furazolidone could be even more efficient than clarithromycin.