BACKGROUND: Prognostic nutritional index (PNI) has recently been identified as a novel marker of nutritional status. However, existing evidences on the association between PNI and the risk of lower extremity deep venous thrombosis (LEDVT) are limited and conflicting. OBJECTIVE: To determine the association between PNI and the risk of LEDVT, and further evaluate its diagnostic value. METHODS: Over a 10-year period (2012-2022), a total of 12790 patients who underwent compression ultrasonography examinations were consecutively included, and 1519 (11.9%) LEDVT events occurred. Multivariate logistic regression analysis was used to investigate the association, and receiver operating characteristic (ROC) curve was constructed to evaluate its diagnostic performance. RESULTS: After full adjustment, patients in third quartile (odds ratio [OR] = 1.486, 95% confidence interval [CI]: 1.205-1.832), second quartile (OR = 2.436, 95% CI: 1.993-2.978) and first quartile (OR = 3.422, 95% CI: 2.791-4.195) of PNI were at higher risk of LEDVT compared with those in fourth quartile, and the test for trend was significant. Consistently, each unit decrease in PNI was associated with a 6.0 % (95% CI: 1.052-1.069) increased risk of LEDVT. Moreover, adding PNI to a base model improved the area under the curve (AUC) from 0.721 (95% CI: 0.709-0.734) to 0.746 (95% CI: 0.734-0.758). CONCLUSION: PNI is inversely associated with the risk of LEDVT, and provides significant incremental diagnostic value for the identification of LEDVT events. These findings suggest that PNI may be a potential biomarker to help clinicians identify patients at risk of thrombosis and make clinical decisions timely.