Abstract: OBJECTIVE To analyze the differences in adverse drug reactions between newborns using medium/long chain fat emulsions and multiple types of oil fat emulsions, and to explore potential risk factors. METHODS A retrospective cohort study was conducted using data from newborns who used medium/long chain fat emulsions or multiple oil fat emulsions from January 2020 to June 2023. The China Hospital Pharmacovigilance System(CHPS) was used to retrieve adverse reaction information and evaluate it. Four hundred and ninety-nine newborns in the medium/long chain fat emulsion group and 1 940 newborns in the multiple oil fat emulsion group were included. Using logistic regression and stratified analysis to explore the safety differences between groups and the risk factors that affect the occurrence of adverse reactions. RESULTS The total incidence of adverse reactions in the medium/long chain fat emulsion group was 19.24%, with common adverse reactions including fever(5.81%), decreased hemoglobin(3.01%), increased blood pressure(2.40%) and hypoglycemia(2.40%); The total incidence of adverse reactions in the group of multiple oil fat emulsions was 36.44%, with a very common adverse reaction being fever(10.57%); common adverse reactions include decreased hemoglobin(8.97%), decreased blood pressure(3.20%), and increased blood pressure(3.09%); rare adverse reactions include liver dysfunction(0.05%), splenomegaly(0.05%) and cyanosis (0.05%). In univariate analysis, the risk of fever, decreased hemoglobin, and increased blood sugar in the group of multiple oil fat emulsions was higher than that in the medium/long chain fat emulsion group(P<0.05), but this association did not show statistical differences in the overall multivariate analysis. Furthermore, a stratified factor analysis based on gestational age found that the risk of fever and decreased hemoglobin in the group of multiple oil fat emulsions was significantly higher than that in the medium/long chain fat emulsion group in extremely premature infants. The corresponding OR(95%CI) were 6.437(1.327, 31.227) and 5.066(1.089, 23.570), respectively, with no significant differences observed in other gestational age stratification. CONCLUSION The risk of using medium/long chain fat emulsions in newborns is similar to that of using multiple types of oil fat emulsions. However, in extremely premature infants, the risk of fever and decreased hemoglobin in multiple types of oil fat emulsions is higher than that in medium/long chain fat emulsions. It is recommended to regularly monitor indicators such as body temperature, hemoglobin, and blood pressure, and do a good job in drug vigilance.