Background and Objective: An optimal regimen for treatment of Helicobacter pylori should have high efficacy, tolerable side effects, easy administration and should be economical. Intensive efforts are being made to identify such an optimal regimen, but there are many obstacles hindering the achievement of this goal. This study aimed at comparing the rate of HP eradication by examining quadruple regimens in dyspeptic patients. Materials and Methods: In this open-label randomized clinical trial, 270 patients with positive Urease test were randomly assigned into four groups to receive one of the following treatment protocols. ( group A: omeprazole+ amoxicillin+ bismuth subcitrate+clarithromycin for 2 weeks (73 patients), group B: omeprazole+tetracycline+bismuth subcitrate+metronidazole for 2 weeks (46 patients), group C: omeprazole+amoxicillin+bismuth subcitrate+furazolidone for 2 weeks (64 patients), groupD: omeprazole+amoxicillin+bismuth subcitrate+furazolidone/metronidazole interchangeably each one for one week (87 patients). Six weeks after the treatment, the compliance, eradication and complication rates were evaluated in each group. Results: Helicobacter pylori eradication rates were, 96.3%, 87%, 79.7%, and 79.3 % in groups A, B, C and D respectively (p=0.506). The overall complication rate was 37%, 63%, 32.8% and 28.7% in groups A, B, C and D respectively. This rate was significantly higher in group B than other groups (p=0.01). The compliance rate was “complete”, ‘good” or “poor”. Accordingly the compliance rate in group A was 83.6%, 11% and 5.5%, in group B, 87%, 6.5% and 6.5%, in group C. 90.6%, 4.7% and 4.7%, and in group D 86.2%, 11.5% and 2.3%, respectively (p=0.683). Abdominal pain and vomiting was significantly more frequent in groups B and C compared to the other groups. The other complications were not significantly different in the groups. Conclusion: The rate of compliance and HP eradication was similar in quadruple regimens however, due to difference in the rate of complications, regimens of groups A or D are recommended.