BACKGROUND AND AIM: Bile acid metabolism plays a crucial role in maintaining the delicate balance between coagulation and anticoagulation processes. However, there is a paucity of research exploring the relationship between serum total bile acids (TBA) levels and the risk of deep venous thrombosis (DVT) in Chinese individuals. The primary objective of this study is to investigate the association between TBA levels and DVT occurrence in this population. METHODS AND RESULTS: A cross-sectional study was conducted involving 4522 patients with suspected DVT, recruited from June 2018 to October 2023, at the First Affiliated Hospital of Xi'an Jiaotong University. After rigorous screening, 3165 patients were included in the final analysis. Participants were categorized into three TBA level groups: low-level (TBA < 2.3 umol/L), moderate-level (2.3 ≤ TBA < 4.3 umol/L), and high-level (TBA ≥ 4.3 umol/L). Logistic regression analysis was utilized to assess the relationship between TBA levels and DVT risk, adjusting for potential confounders. The median age of the study population was 63 years, with a median TBA level of 3.2 (1.9-5.3) umol/L. The findings revealed that, compared to the low-level TBA group, the moderate and high-level TBA groups had significantly higher odds ratios (ORs) for DVT, with ORs of 1.47 (95% CI: 1.21 to 1.78, P < 0.001) and 1.91 (95% CI: 1.58 to 2.32, P < 0.001), respectively. Interestingly, higher TBA levels were also associated with reduced odds of bleeding risk, with ORs of 0.81 (95% CI: 0.63 to 1.03, P < 0.001) and 0.64 (95% CI: 0.5 to 0.81, P < 0.001), respectively. CONCLUSIONS: Our study provides evidence that serum TBA levels may serve as a risk factor for DVT in Chinese individuals, with higher levels conferring an increased risk. Additionally, unexpectedly, higher TBA levels were found to be associated with a reduced risk of bleeding complications. These findings have significant implications for understanding the complex interplay between bile acid metabolism and deep venous thrombosis, and warrant further investigation.