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Introduction: Furazolidone has been introduced as an effective drug against helicobacter pylori infection in Iran, but intolerable side-effects may limit its use. We compared quadruple and triple furazolidone-based regimens to achieve an economically affordable regimen with acceptable efficacy rate and fewer complications. Matherials & Methods: Patients with H.pylori positive peptic ulcer disease were randomly divided into two groups. They were treated with amoxicillin 1gm/BID, furazolidone 200 mg/BID, omeprazole 20mg/BID with and without bismuth sub-citrate 240 mg/BID for two weeks (AFOB & AFO regimens, respectively) H.pylori eradication was confirmed by 13C-urea breath test 12 weeks after the end of the treatment. Findings: Eighty six patients were enrolled but 16 ones discontinued their therapy or follow-up. The eradication rates in AFOB & AFO were 85.3% and 61.1% by per-protocol analysis, respectively (P=0.02), and 67.4% & 51.2% by intention–to-treat analysis respectively (P<0.05). The most frequent adverse effects in the two study groups were weakness, nausea, anorexia and dizziness that demonstrated no significant differences. Discussion & Conclusion: In this study, furazolidone-based triple therapy (without bismuth) was not recommended for H.pylori eradication, due to the lower eradication rate and unchanged frequency of adverse effects.