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Background: Furazolidone has recently shown promising efficacy in H. pylori eradication and has replaced metronidazole in different eradication regimens especially in countries, like Iran, with high prevalence of metronidazole resistance and where clarithromycin is expensive and hardly available. This study tries to determine the efficacy of a quadruple therapy based on furazolidone as a second line treatment., Material/methods: 90 consecutive patients with a prior history of H. pylori infection who had failed to respond to a 14 day course of metronidazole-based quadruple therapy were included to take a two week quadruple therapy consisting of furazolidone, bismuth subcitrate, amoxicillin and omeprazole. Eradication was described as negative 14C-urea breath test, 4 to 6 weeks after end of the treatment., Results: 89 of 90 patients completed the treatment course. The total eradication rate was 70/89 (78.7%). 35/49 (71.4%) of male patients and 35/40 (87.5%) of female patients had successful eradication. Eradication rate did not have any significant relationship with patient's sex (p>0.05). All patients had at least one upper GI endoscopy before the treatment by which they were categorised into three groups: duodenal ulcer (DU, 78.9%), gastric ulcer(GU, 11.1%) and non-ulcer dyspepsia (NUD, 10%). Eradication rates was different in these groups, but not significantly (p>0.05). Eradication rate was significantly lower in smokers (p<0.05, OR=3.12)., Conclusions: Furazolidone can replace metronidazole successfully in those patients who have failed to respond to metronidazole-based quadruple therapy and it is well tolerated. We recommend it, especially in countries where clarithromycin is expensive or not available.