【Objective】To evaluate the efficacy and safety of quadruple therapy based on moxifloxacin and bismuth in the treatment of Helicobacter pylori eradication failure.【Methods】A prospective，randomized，comparative study was conducted in which 136 eligible patients were randomly divided into the extended quadruple group（66 patients，and the quadruplex therapies are Pectin bismuth 100 mg tid + lansoprazole 30 mg bid + amoxicillin 1000 mg bid + moxifloxacin 400 mg qd）and the classical quadruple group（70 patients，and the quadruple therapies are colloidal pectin bismuth 100 mg tid + lansoprazole 30 mg bid + tetracycline tablet 750 mg Bid + metronidazole tablets 400 mg bid combination）and were under treatment for 14 days. One month after the treatment，endoscopy，rapid urease test，and 13-carbon / 14-carbon urease breath test were used to evaluate the adverse effects and adherence of the drugs in the two groups respectively.【Results】In the extended quadruple group，among 60 patients who had completed the final treatment and follow-up survey，55 were successfully treated，with eradication rates of（83.3%，55/66） and 91.7%（55/60）according to intention-to-treat（ITT）and Per-protocol（PP）respectively. In the classic quadruple group，64 patients completed the final treatment and follow-up survey. Among them，37 cases were successful，and the eradication rates according to ITT and PP remedy are 52.9%（37/70）and 57.8%（37/64）respectively. The difference was statistically significant（P < 0.001）. Adverse drug reactions and compliance monitoring showed no significant difference between the two groups（P > 0.05）. 【Conclusion】The quadruple therapy based on moxifloxacin and bismuth displays a higher eradication rate than that of the classical bismuth quadruple therapy on the first-time elimination failure of Helicobacter pylori while shows no difference in safety consideration， thus can serve as remedial therapy for the primary Hp eradication failure.