Background & Aim: Metronidazole-based quadruple therapy is widely used by physicians as the first line regimen for eradication of helicobacter pylori(H.pylori) in Iran. However, high rate of metronidazole resistance in Iran casts doubt on the efficacy of such regimens in this country. In this respect, this study tries to determine the efficacy of a quadruple therapy based on metronidazole as the first line treatment of H.pylori. Patients & Method: Two hundred fifty-eight patients with peptic ulcer and proven H.pylori infection were included to take a two-week quadruple therapy consisting of metronidazole, bismuth subcitrate, amoxicillin and omeprazole followed by an additional two-week course of omeprazole. Eradication was described as negative 13C-urea breath test(UBT) one month after the completion of the treatment. Results: The patients’ mean age was 45 years and 64.1% of the subjects were female. Seven patients could not complete the treatment course because of intolerable treatment side effects. Eradication rate was 34.9% based on intention-to treat analysis and 35.9% based on protocol analysis. Conclusion: Quadruple therapy based on metronidazole and amoxicillin has limited efficacy in Iran and should not be used for eradication of H.pylori in this country.