Objective To evaluate the efficacy， safety and patient compliance of a quadruple therapy containing minocycline compared with the traditional quadruple therapy in the treatment of Helicobacter （H.） pylori. Methods This study included 200 H.pylori positive patients， with 100 assigned to the minocycline-containing bismuth quadruple therapy group （LBMC group） and the other 100 to the amoxicillin-containing bismuth quadruple therapy group （LBAC group）. After matching the two groups of patients using the propensity score matching （PSM） method，there were 86 cases in each group. Telephone follow-up was conducted on the 14^th day after the start of treatment to record patient medication compliance and adverse drug reactions. A ¹³C urea breath test was performed for re-examination at least one month after completing the treatment plan and discontinuing medication.The intention-to-treat （ITT） and per-protocol （PP） analyses were used to compare the H.pylori eradication rates between the two groups， and Chi-square test and t-test were used for intergroup comparison. Results In the ITT analysis， the eradication rates of the LBMC group and the LBAC group were 89.5% （77/86， 95%CI： 82.9% ~ 96.1%） and 82.6% （71/86， 95%CI： 74.4% ~ 90.7%）， respectively. In the PP analysis，the eradication rates were 92.6% （75/81， 95%CI： 86.8% ~ 98.4%） and 88.8% （71/80， 95%CI： 81.7% ~ 95.8%）， respectively. The adverse reaction rate of the LBMC group was 27.9% （24/86）， and that of the LBAC group 31.4% （27/86）， showing no statistically significant difference （P > 0.05）. In terms of compliance， the LBMC group was 94.2% （81/86）， and the LBAC group 93.0% （80/86）， revealing no statistically significant difference （P > 0.05）. Conclusion As a first-line treatment for eradicating H.pylori， regimens containing minocycline demonstrate equivalent eradication rates to those containing amoxicillin， with similar safety and compliance. They can be used as an alternative treatment for patients allergic to penicillin.