Abstract: Objective The present study aimed to provide some reference for further refinement of China's Essential Medicines List by comparing the similarities and differences in antimicrobial drugs between the 2018 edition of the National Essential Medicines List (NEML 2018) and the 2025 edition of the World Health Organization's Model List of Essential Medicines (EML 2025). Methods Descriptive analysis was employed to compare the differences in antimicrobial drugs across the two directories, focusing on variety, AwaRe classification, and quantity. Results Compared to EML 2025, NEML 2018 includes fewer antimicrobial drug varieties and exhibits higher consistency in core antimicrobial drug selection, yet with deficiencies in drugs for multidrug-resistant bacteria treatment and novel antimicrobial agents, with limited inclusion of reserve-category drugs, an insufficient supply of dosage forms suitable for special populations, and a narrow range of available strengths. Conclusion The antimicrobial drugs section of NEML 2018 should be enriched to address the challenges of antimicrobial resistance and meet the needs of specific populations, with room for improvement, particularly in ensuring clinical efficacy, enhancing medication safety, and optimizing long-term cost-effectiveness. EML 2025 is recommended for reference to refine the product portfolio, increase options for treating resistance and include novel antimicrobial agents, and supplement appropriate dosage forms and strengths, so as to help enhance the rationality, safety, and accessibility of clinical medication use.