Abstract: AIM: Through the Monte Carlo simulation to monitor the change of MIC in late-onset sepsis of gram-positive cocci in neonates, through the cumulative fraction of response to evaluate the changing trend of bacterial resistance in our center and analyze the possibility of inducing drug resistance of bacterial, to reduce the occurrence of bacterial drug resistance in clinical work.  METHODS: This study retrospectively investigated the basic information, pathogen species and drug sensitivity results of neonatal late-onset sepsis of gram-positive cocci in Neonatal Intensive Care Units of Beijing Maternity Hospital from 2016 to 2019, and divided them into four groups by year. Crystal ball software was used to calculate the annual CFR of sensitive antibiotics (Vancomycin) against the gram-positive cocci by Monte Carlo simulation. RESULTS: From 2016 to 2019, there were 58 cases of late-onset sepsis caused by gram-positive cocci in neonates, and the number of pathogens detected each year showed no significant change, and there was no statistical difference in the affected population each year. Among them, the top three were 31 strains of Staphylococcus epidermidis (53.5%), 9 strains of Enterococcus faecium (15.5%), and 6 strains of Enterococcus faecalis (10.3%). Drug sensitivity tests showed that the resistance rates of Staphylococcus epidermidis, Enterococcus faecium and Enterococcus faecalis to Vancomycin and Linezolid were 0%. The CFR of Vancomycin against gram-positive cocci from 2016 to 2019 calculated by Monte Carlo simulation were 82%, 88.72%, 81.73% and 78.53%, respectively, which showed a downward trend. CONCLUSION: By using Monte Carlo simulation method, CFR can reflect the change of bacterial drug resistance with drug sensitivity test as the standard, and evaluate the current treatment plan, which should be paid attention to in clinical work.