Purpose: Bloodstream infections (BSIs) are a common consequence of infectious diseases and cause high morbidity and mortality. Appropriate antibiotic use is critical for patients' treatment and prognosis. Long-term monitoring and analysis of antimicrobial resistance are important in guiding physicians to choose appropriate antibiotics and understand the changes in antimicrobial resistance and infection control. Here, we report a retrospective study on the trends of antimicrobial resistance in the common BSI-associated pathogens. Methods: The identification of strains and antimicrobial susceptibility tests were performed in each anticipating hospital indepen-dently. Data from the Hubei Province Antimicrobial Resistance Surveillance System (HBARSS) from 1998 to 2017 were retro-spectively analyzed using WHONET 5.6 software. Results: Data from HBARSS (1998-2017) revealed that 40,518 Gram-positive bacteria and 26,568 Gram-negative bacteria caused BSIs, the most common of which were Staphylococcus aureus and Escherichia coli. Salmonella typhi was a predominant BSI-associated pathogen in 1998-2003. Antimicrobial susceptibility data showed that the resistance rates of E. coli and Klebsiella pneumoniae to cefotaxime were significantly higher than those to ceftazidime. The proportion of strains of special antimicrobial resistance phenotypes including difficult-to-treat resistance (DTR), carbapenem-resistant (CR), extended-spectrum cephalosporin resistant (ECR) and fluoroquinolone resistant (FQR) in E. coli was 0.18%, 0.26%, 13.95%, 22.78% while in K. pneumoniae was 11.95%, 14.00%, 31.91% and 11.40%, respectively. In 2013-2017, K. pneumoniae showed resistance levels reaching 15.8% and 17.5% to imipenem and meropenem, respectively, and Acinetobacter baumannii showed high resistance rates ranging from 60 to 80% to common antibiotics. The detection rate of Salmonella typhi resistance to third-generation cephalosporins and fluoroquinolones was less than 5%. Control of methicillin-resistant Staphylococcus aureus (MRSA) remains a major challenge, and in 2009-2017, the MRSA detection rate was 40-50%. Conclusion: Prevalence of CR K. pneumoniae has increased significantly in recent years. Resistance rates of A. baumannii to common antimicrobial agents have increased exponentially, reaching high levels. MRSA remains a challenge to control. For K. pneumoniae, DTR, CR, ECR and FQR were antimicrobial resistance phenotypes that could not be ignored while for E. coli DTR and CR were rare antimicrobial resistance phenotypes. CR K. pneumoniae, A. baumannii and MRSA present major challenges for controlling BSIs.