Objective To compare the impact of two types of fat emulsion on clinical outcomes in preterm infants with varying duration of parenteral nutrition (PN). Methods Preterm infants meeting the inclusion criteria were randomly assigned to two groups: medium/long-chain triglyceride fat emulsion (referred to as MCT/LCT) group or multi-oil fat emulsion (containing soybean oil, medium-chain triglycerides, olive oil, and fish oil; referred to as SMOF) group. The infants were stratified into groups based on the duration of PN (15-21 days, 22-28 days, and ≥29 days). Clinical characteristics, nutritional status, biochemical indicators, and clinical outcomes were compared between the two groups. Results Compared with the MCT/LCT group, the SMOF group had lower peak levels of triglyceride during the hospital stay in preterm infants with PN of 15-21 days, 22-28 days, and ≥29 days, respectively (P<0.05). Logistic regression trend analysis showed that with a longer duration of PN, the risk of parenteral nutrition-associated cholestasis (PNAC) and bronchopulmonary dysplasia (BPD) significantly increased in the MCT/LCT group (P<0.05), while the risk of brain injury did not significantly change (P>0.05). In the SMOF group, the risks of PNAC and BPD did not significantly change with a longer duration of PN (P>0.05), but the risk of brain injury significantly decreased (P=0.006). Conclusions Compared to MCT/LCT, SMOF have better lipid tolerance. With a longer duration of PN, SMOF does not increase the risks of PNAC and BPD and had a protective effect against brain injury. This suggests that in preterm infants requiring long-term PN, the use of SMOF is superior to MCT/LCT.