BACKGROUND: No large-scale, multicenter studies have explored the incidence rate and predictors of deep vein thrombosis (DVT) in patients with acute ischemic stroke (AIS). We aimed to determine the risk factors of DVT, and assess the association between DVT and clinical outcomes in AIS patients. METHODS: In total, 106,612 patients with AIS enrolled in the Chinese Stroke Center Alliance between August 2015 and July 2019 were included. The predictors of DVT in AIS patients were screened based on the logistic regression analysis for the comparison of the characteristics and clinical outcomes of patients with and without DVT. RESULTS: The overall incidence of DVT after AIS was 4.7%. Factors associated with increased incidence of DVT included advanced age, female sex, high admission National Institutes of Health Stroke Scale score, history of cerebral hemorrhage, transient ischemic attack (TIA), dyslipidemia, atrial fibrillation, and peripheral vascular disease, International Normalized Ratio (INR) <0.8 or >1.5, and blood uric acid >420 μmol/L. Ambulation and early antithrombotic therapy were associated with a lower incidence of DVT. Patients with DVT was associated with longer hospital stay (OR=1.44, 95% CI: 1.35-1.54), and higher in-hospital mortality (OR=1.68, 95% CI: 1.25-2.27). CONCLUSIONS: This large-scale, multi-center study showed that the occurrence of DVT in AIS patients is associated with various modifiable and objective indicators, such as abnormal INR and uric acid >420 μmol/L. Ambulatory status and early antithrombotic therapy can reduce the occurrence of DVT in AIS patients. In AIS patients, DVT may prolong the hospital stay and increase the risk of in-hospital mortality. Future research should focus on the clinical implementation of existing evidence on DVT prevention in AIS patients.