Abstract Background: The eradication rate of the standard bismuth-containing quadruple therapy for Helicobacter pylori infection has gradually decreased in China, even patients don't receive antibiotics with high resistance and have good compliance.Objective: To investigate why patients experienced standard bismuth-containing quadruple therapy (not include clarithromycin, metronidazole and levofloxacin) with good compliance still eradication failure, we performed a retrospective, single center study to identify causes of treatment failure.Methods: Patients with H.pylori infection who were treated with standard bismuth-containing quadruple therapy (not include clarithromycin, metronidazole and levofloxacin) and received a test of cure at The third xiangya hospital between Oct. 2017 and May. 2021 were enrolled. Demographic and clinical data were recorded. Eradication rates were calculated and compared between regimens and subgroups. Logistic regression analysis was performed to identify risk factors of eradication failure. Results: nine hundred and seventy five patients were included in the final analysis, 891 patients were successful eradicated, the total successful eradication rate was 91.4%. The quadruple therapy containing amoxicillin plus doxycycline achieved the highest eradication rate (93.0%), followed by therapy that consisted of amoxicillin plus furazolidone (92.1%) and doxycycline plus furazolidone (90.8%). There was no significant difference in the eradication rate between these groups. Logistic regression analysis found that male (OR：1.984；95%CI：1.176-3.345), 45-years old and above (OR：2.902；95%CI：1.628-5.171) were associated with an increased risk of eradication failure. In primary therapy, Male (OR：2.085；95%CI：1.188-3.658), 45-years old and above (OR：3.072；95%CI：1.659-5.688), the history of antibiotic abuse (OR：2.624；95%CI：1.267-5.436) and eating out (OR：1.923；95%CI：1.034-3.577) were associated with an increased risk of eradication failure.Conclusions: Male, aged (≥45years old) are factors affecting H.pylori eradication failure in patients don't receive antibiotics with high resistance and have good compliance. Male, aged (≥45years old), the history of antibiotic abuse and eating out are factors affecting H.pylori primary eradication failure in patients don't receive antibiotics with high resistance and have good compliance.