Abstract: OBJECTIVE To analyze the risk factors and pathogen distribution characteristics of mortality in patients with secondary bloodstream infection. METHODS Data from 340 patients diagnosed with secondary bloodstream infection at the First Affiliated Hospital of Nanjing Medical University from Jan. 2020 to Dec. 2024 were retrieved through the Xinglin Nosocomial Infection Surveillance. Patients were divided into a survival group and a mortality group based on their prognostic outcomes. The distribution characteristics of pathogens in secondary bloodstream infection from different infection sources were analyzed. Univariate and multivariate COX regression analyses were conducted to identify risk factors for mortality in secondary bloodstream infection. RESULTS Significant differences were observed in the distribution of pathogens and key monitored bacteria in secondary bloodstream infection from different infection sources. Abdominal infection sources were predominantly associated with Escherichia coli (31.11%), Klebsiella pneumoniae (26.67%) and Enterococcus faecium (12.59%). Lower respiratory tract infection sources were mainly linked to K. pneumoniae (33.33%), Acinetobacter baumannii (26.67%) and Pseudomonas aeruginosa (8.57%). Urinary tract infection sources were primarily associated with E. coli (35.29%), K. pneumoniae (23.53%), E. faecalis and E. faecium (both 7.35%). The detection rate of key monitored bacteria was higher in lower respiratory tract infection (62.86%) than in abdominal infection (24.44%) and urinary tract infection (14.71%). Multivariate COX regression analysis revealed that age (≥60 years) (HR=1.857, 95%CI: 1.206-2.858), infection with key monitored bacteria (HR=1.583, 95%CI: 1.047-2.392), secondary source (lower respiratory tract infection) (HR=2.217, 95%CI: 1.340-3.667), creatinine (HR=1.001, 95%CI: 1.000-1.002) and albumin-bilirubin score (ALBI) grade (Grade 3) (HR=2.911, 95%CI: 1.337-6.335) were risk factors for mortality in secondary bloodstream infection, with statistically significant differences (all P<0.05). CONCLUSIONS The characteristics of pathogens vary among different secondary bloodstream infections. Advanced age, infection with key monitored bacteria, secondary lower respiratory tract infection, elevated creatinine levels and abnormal liver function are risk factors for mortality. Close attention should be paid to these factors, and targeted diagnostic, therapeutic and preventive strategies should be implemented.