<p>This study used prescription data from four medical institutions in representative cities in Central, Western and Eastern China, focusing on changes in antibiotic use under the National Centralized Drug Procurement Policy (NCDP) and calculating the contribution of NCDP and non-NCDP varieties to the changes. In outpatient settings, NCDP policy had little impact on the antibiotic prescription rate. Changes in antibiotic utilization rates were predominantly driven by non-NCDP varieties, particularly newer-generation antibiotics with enhanced therapeutic profiles. However, the policy more effectively facilitated the substitution of non-NCDP varieties with NCDP varieties in inpatient settings compared to outpatient settings. The overall and injectable antibiotic utilization rates remained within the specified range and continued to decline, although the downward trend was more gradual compared to the pre-intervention period. In conclusion, the substitution effect of NCDP varieties has affected antibiotic usage in inpatient settings, directly influencing both the overall antibiotic prescription rate and the prescription rate of injectable antibiotics. Therefore, for optimizing antibiotic stewardship under China’s NCDP policy, regular monitoring and managing of antibiotics is essential to ensure the rational use of antibiotics.</p>