Abstract: OBJECTIVE To observe the curative effect of Helicobacter pylori(Hp) eradication with different drug quadruple regimen. METHODS Patients with Hp infection for initial and remedial treatment(180 cases respectively) were randomly divided into four groups, initial treatment group(treated with amoxicillin capsule+doxycycline capsule), initial treatment control group(treated with amoxicillin capsule+clarithromycin tablet), remedial treatment test group(treated with amoxicillin capsule+doxycycline capsule), remedial treatment control group(treated with amoxicillin capsule+levofloxacin tablet), each group were combined with esomeprazole enteric coated tablets, colloidal bismuth pectin capsule, twice a day, treat for 14 d. After 4 weeks of treatment, ¹³C breath test was reexamined, Hp eradication rate, adverse reactions, cost-effectiveness ratio(C/E) were observed, and Hp recurrence rate was observed after 6 or 12 months of follow-up. RESULTS In the Hp initial treatment group, there was no significant difference in the eradication rate and recurrence rate between initial treatment test group and control group, but the C/E of initial treatment test group was lower. In the Hp remedial treatment group, the Hp eradication rate of remedial treatment test group was higher than that of remedial treatment control group, and the curative effect was better, the difference was statistically significant(P<0.05), the C/E was lower, and the recurrence rate was lower, the difference was not statistically significant. In comparison of adverse reactions in each group, the incidence of adverse reactions in initial treatment test group, remedial treatment test group and remedial treatment control group was lower than initial treatment control group, the difference was statistically significant(P<0.01). CONCLUSION The quadruple regimen combination of doxycycline and amoxicillin has a better short-term and long-term effect and lower cost in eradicating Hp.