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Portal vein thrombosis in cirrhotic patients presents a significant clinical challenge. This study aims to (1) explore the impact of anticoagulation therapy on patient outcomes; (2) comparative outcomes in portal vein thrombosis treated between direct oral anticoagulant and Vitamin K Antagonist (VKA). We leveraged the TriNetX database to analyze a cohort comprising 4224 patients with liver cirrhosis and PVT who were treated with anticoagulation, alongside a comparison group of 15,300 patients with the same conditions but not receiving anticoagulation therapy. The anticoagulated group showed a significant reduction in mortality (27.9 % vs. 34.2 %, HR = 0.723, 95 % CI: 0.678–0.770, P < 0.001). When comparing direct oral anticoagulant versus. VKA, in compensated liver cirrhosis, the direct oral anticoagulant group exhibited significantly lower mortality rates compared to VKA (17.7 % vs. 26.5 %, HR = 0.655, 95 % CI: 0.452–0.951, P = 0.025), with no significant difference in liver transplantation rates (4.0 % vs. 4.7 %, P = 0.080). In decompensated liver cirrhosis, the direct oral anticoagulant group exhibited lower mortality compared to the VKA group (23.6 % vs. 30.6 %, HR = 0.732, 95 % CI: 0.629–0.851, P < 0.001), and a higher frequency of liver transplantation was observed in the VKA group (10.6 % vs. 16.0 %, HR = 0.622, 95 % CI: 0.494–0.784, P < 0.001). Hospitalization rates were significantly lower in the direct oral anticoagulant group compared to the VKA group in decompensated cirrhosis (33.4 % vs. 38.3 %, HR = 0.830, 95 % CI: 0.695–0.992, P = 1.937). Our study offers compelling evidence supporting the use of anticoagulation therapy in liver cirrhosis with portal vein thrombosis. The use of DOACs in patients with both compensated and decompensated liver cirrhosis showed a marked mortality benefit. • Significant reduction in mortality among patients with cirrhosis and portal vein thrombosis treated with anticoagulants. • Patients with cirrhosis show better survival on DOACs than on VKAs. • Similar major bleeding rates in decompensated cirrhosis with DOACs vs. VKAs. • No significant mortality difference in decompensated cirrhosis between DOACs, VKA. • Lower hospital stays for cirrhosis patients on DOACs boost healthcare efficiency. [ABSTRACT FROM AUTHOR]