Abstract: OBJECTIVE To explore the effects of fluoroquinolone substitution regimens for rifampicin and standard rifampicin-resistant regimens on treatment of the patients with rifampicin-resistant tuberculosis. METHODS A total of 571 patients with rifampicin-resistant tuberculosis who were treated in Beijing Chest Hospital Affiliated to Capital Medical University, Nanning Fourth People's Hospital and Fourth Hospital of Inner Mongolia Autonomous Region from Jan. 1, 2013 to Dec. 31, 2024 were recruited as the research subjects. Comparable cohorts were constructed by means of propensity score matching (PSM), the primary endpoints were taken as the treatment success rate, and the non-inferiority was evaluated through confidence interval method. RESULTS The PSM was carried out in a 1∶3 ratio for the experimental group and the control group. There were 34 patients in the experimental group and 133 patients in the control group after the 571 patients were matched. The baseline characteristics of the two groups presented high degree of balance. The result of between-group comparison of treatment success rate showed that there were totally 16 cases of favorable outcomes in the experimental group after the matching, with the success rate 47.06%(16/34); there were 83 cases of favorable outcomes in the control group, with the success rate 62.40%(83/133); there was no significant difference in the success rate between the two groups (χ²=2.642,P=0.104). The lower limit of 95% confidence interval of the rate difference between the experimental group and the control group was higher than 15%. With the respect to the adverse reactions, there were no significant differences in the indicators such as the white blood cells, platelets, hemoglobin, and hepatorenal function between the two groups. CONCLUSION Among the patients with rifampicin-resistant tuberculosis, only substitution for rifampicin with other first-line drugs preserved may not be inferior to the standard rifampicin-resistant regimen, with the safety basically same.