Abstract: OBJECTIVE To observe the influence of empirical antibiotic therapy on 28-day mortality of the bloodstream infections patients with varying clinical characteristics so as to provide bases for optimizing of clinical use of antibiotics and seizing the treatment timing. METHODS A retrospective survey was conducted on the clinical data of 528 patients with bloodstream infections who were treated in Xijing Hospital, The Fourth Military Medical University from Jul. 2018 to Feb. 2023. The enrolled patients were divided into the appropriate group with 354 cases and the inappropriate group with 174 cases according to the accuracy of selection of empirical antibiotics. The clinical characteristics and the influence of appropriate empirical therapy on the 28-day mortality rate of the patients with different clinical characteristics were observed and compared between the two groups. RESULTS The proportion of patients with health care-associated infections was higher in the inappropriate group (67.24%) than in the appropriate group, while the proportion of patients with community-associated infections was lower in the inappropriate group (17.24%) than in the appropriate group; the incidence of Escherichia coli infection was lower in the inappropriate group (16.09%) than in the appropriate group; the incidence of Acinetobacter baumannii infection was higher in the inappropriate group (14.37%) than in the appropriate group, and there were significant differences (P＜0.05). The proportions of patients complicated with heart failure, moderate-severe renal disease, secondary pulmonary infections, the incidence of multidrug-resistant organisms infections and the 28-day mortality rate were higher in the inappropriate group than in the appropriate group (P＜0.05). As for the sensitive E. coli, the appropriate empirical therapy could reduce the risk of 28-day mortality for the patients with mild complications and the patients with community-associated infections as well as the patients with health care-associated infections (P＜0.05). CONCLUSION The empirical antimicrobial therapy may not always improve the prognosis of all the patients, and it is necessary to scientifically determine the timing of antibiotic administration and implement individualized treatment strategies.