Background <p>Overt hepatic encephalopathy (OHE) is a common complication following transjugular intrahepatic portosystemic shunt (TIPS) procedures in patients with cirrhosis.</p> <p>However, the relationship between preoperative triglyceride (TG) levels and post-TIPS OHE risk remains unclear. This study aimed to investigate whether elevated preoperative TG levels are independently associated with increased risk of developing OHE following TIPS in patients with cirrhosis.</p> Methods <p>This retrospective cohort study included 172 patients with cirrhosis who underwent TIPS at Yichang Central People's Hospital from January 2021 to December 2023. The primary exposure variable was preoperative TG level, and the primary outcome was the occurrence of OHE during follow-up. Cox proportional hazards regression models were used to analyze the relationship between TG levels and OHE risk, with stratified analyses conducted according to Child-Pugh classification and blood ammonia levels.</p> Results <p>The incidence of OHE was significantly higher in the high TG group compared to the low TG group (45.2% vs 26.1%, P=0.026). After adjusting for multiple confounding factors, each 1 mmol/L increase in TG was associated with a 15.4% increase in OHE risk (HR=1.154, 95% CI: 1.042-1.426, P=0.036). Compared to the lowest quartile TG group, the highest quartile group showed a 26.5% increase in OHE risk (HR=1.265, 95% CI: 1.201-1.461, P=0.001). This association was more pronounced in patients with Child-Pugh class B/C. </p> Conclusions <p>Elevated preoperative TG levels are independently associated with increased risk of post-TIPS OHE development. Preoperative TG level assessment may help identify high-risk patients and facilitate the development of appropriate preventive strategies.</p>