Objective To analyze the correlation between the drug resistance rate of common pathogens in blood culture of inpatients from the First Hospital Affiliated to Hebei North University from 2019 to 2021 and the frequency of antimicrobial drug use (DDDs). Methods Strains isolated from positive blood cultures of inpatients from 2019 to 2021 were collected, and data on antimicrobial drug use in patients with positive blood cultures during the same period were also collected. WHONET 5.6 software and Pearson correlation analysis were used to explore the correlation between pathogenic bacterial resistance rate and antimicrobial DDDs. Results A total of 916 samples tested positive in blood cultures from 2019 to 2021. Among the top antimicrobial drugs in DDDs, the DDDs of cefazolin, cefuroxime, and ceftazidime all showed an upward trend year by year (the increase from 2019 to 2021 was 38.8%, 228.3%, and 87.1%, respectively). A total of 739 pathogenic bacteria strains were isolated from positive blood culture samples from 2019 to 2021, and the top five pathogenic bacteria were Escherichia coli, Klebsiella pneumoniae, Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa, accounting for 37.2%, 16.1%, 8.1%, 7.4%, and 6.5%, respectively. The drug resistance rates of Escherichia coli to cefazolin, ceftazidime, cefotaxime, and polymyxin B were positively correlated with their DDDs (r=0.961, 0.907, 0.988, 0.997, P < 0.05). The drug resistance rates of Klebsiella pneumoniae to piperacillin, cefazolin, cefotaxime, cefepime, aztreonam, imipenem, meropenem, levofloxacin, and polymyxin B were positively correlated with their DDDs (r=0.766, 0.772, 0.838, 0.667, 0.734, 0.821, 0.904, 0.980, 0.997, P < 0.05). The drug resistance rate of Pseudomonas aeruginosa to gentamicin was positively correlated with their DDDs (r=0.878, P < 0.05). The drug resistance rate of Acinetobacter baumannii to moxifloxacin was positively correlated with its DDDs (r=0.856, P < 0.05). However, there was no correlation between the drug resistance rates of Staphylococcus aureus and Staphylococcus epidermidis to most commonly used antimicrobial drugs and antimicrobial DDDs (P>0.05). Conclusion The pathogenic bacteria causing bloodstream infections in inpatients at the First Hospital Affiliated to Hebei North University from 2019 to 2021 are complex and diverse (mainly Gram-negative bacteria). The overall drug resistance rate of pathogenic bacteria shows an upward trend, and there is a correlation between the drug resistance rates of most pathogenic bacteria and antimicrobial DDDs.