Abstract: Objective To analyze the distribution characteristics of pathogenis bacteria in blood cultures and changes in drug resistance in a tertiary teaching hospital in the past ten years, in order to provide evidence for the rational use of antimicrobial drugs and prevention and control of bloodstream infections. Methods Blood culture-positive patients who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2014 to December 2023 were selected, and the species and drug resistance of pathogenic bacteria isolated from clinical blood specimens were collected. The trend of drug resistance changes of major pathogenic bacteria in blood cultures between 2014—2018 and 2019—2023 were compared. Results A total of 11 578 strains of bacteria were detected in blood cultures from 2014—2023, where 6 196 strains (53.5%) were gram-positive and 5 382 strains (46.5%) were gram-negative. The gram-positive bacteria were mainly coagulase-negative staphylococci (4 302 strains, 37.2%) and Staphylococcus aureus (704 strains, 6.1%), Enterococcus faecalis (352 strains, 3.0%), and Enterococcus faecalis (208 strains, 1.8%). The gram-negative bacteria were mainly Escherichia coli (2 355 strains, 20.3%), Klebsiella pneumoniae (1 095 strains, 9.5%), Acinetobacter baumannii (447 strains, 3.9%), and Pseudomonas aeruginosa (391 strains, 3.4%). The pathogenic bacteria were mainly distributed in the general intensive care unit (ICU) (1 702 strains, 14.7%), emergency ICU (1 436 strains, 12.4%), Department of Hematology (1 134 strains, 9.8%), and Department of Infectious Diseases (758 strains, 6.5%). The resistance rates of Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli to imipenem were 85.2%, 18.2%, 26.0% and 4.0%, respectively, and their resistance rates to meropenem were 85.2%, 12.7%, 29.4% and 4.0%, respectively. Staphylococcus aureus and coagulase-negative staphylococci had oxacillin resistance rates of 56.8% and 80.4%, respectively, and no staphylococci were found to be vancomycin-resistant. The resistance rates of Enterococcus faecalis and Enterococcus faecalis to vancomycin were 0.5% and 1.1%, respectively. Compared with 2014-2018, the resistance rates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae to carbapenem antimicrobials increased in 2019-2023; the resistance rates of Staphylococcus aureus to benzoxacillin and Enterococcus faecalis to vancomycin decreased, but the differences were not statistically significant(P＞0.05); and the resistance rate of Escherichia coli to imipenem decreased from 5.2% to 3.0%, and the differences were statistically significant(P＜0.05). Conclusions The drug-resistant situation of common pathogenic bacteria in blood cultures in our hospital is still severe, and we should continue to standardize the collection and delivery of blood culture specimens, select appropriate antimicrobial drugs according to the results of drug sensitivity, promote the rational use of antimicrobial drugs, and work together to curb drug resistance.