Background: Nosocomial bloodstream infection (BSI) remains a significant cause of mortality , morbidity. We evaluate the trend of the pathogens of nosocomial BSI and inves-tigate the distribution of the pathogens to demonstrate the risk factors of mortality.Methods: In this retrospective study, we collected data from a 2076-bed tertiary referral cen-ter that offers a full range of clinical services in central Taiwan during January, 2016 to December, 2017.Results: Five hundred and eighty-four patients were identified with nosocomial BSI. Among the comorbidities of nosocomial BSI patients with, the most frequent were hypertension, in 294 patients (50.3%), malignancy, in 279 patients (47.8%); diabetes, in 278 patients (47.6%); chronic kidney disease, in 171 patients (29.3%); and liver cirrhosis, in 132 patients (22.6%). Gram-positive organisms caused 22.9% of these nosocomial BSIs, gram-negative organisms caused 69.2% , fungi caused 6.8%. The most common organism causing nosocomial BSIs were Klebsiella spp. (14%), E coli. (14%), and Enterococcus spp. (11%). Multivariate analysis of risk factors for mortality displayed that comorbidity with low body weight, liver cirrhosis, and malignancy, high CRP level, high Charlson Comorbidity Index and internal medicine and hematology/oncology distribution were strikingly associated with mortality (P = 0.0222, 0.0352, 0.0008, 0.0122, <0.001, and 0.041; [OR] = 1.8097, 1.9268, 2.7156, 2.7585, 3.5431, and 2.2449, respectively).