Background: Portal vein thrombosis (PVT) is the most common vascular disease of the liver and a well-known complication in patients with liver cirrhosis with potential severe consequences. However, studies on the course and outcome of PVT are limited. This study assessed the course and outcome of PVT, especially focusing on the impact of anticoagulation. Patients and Methods: This is a retrospective analysis of 126 patients diagnosed with PVT between 01/1997 and 06/2016. 72 (57.1%) and 54 (42.9%) patients presented with malignant PVT and non-malignant PVT, respectively. Overall, 117 patients (92.9%) developed PVT in presence of liver cirrhosis, while 8 patients were diagnosed with non-malignant, non-cirrhotic PVT. One single patient was diagnosed with non-cirrhotic, malignant PVT. Laboratory parameters were collected at a timepoint prior to PVT diagnosis, at diagnosis, and at follow-up, respectively. Course of PVT was evaluated based on radiologic imaging reports. Results: Patients with malignant PVT show a significantly shorter overall survival than patients with non-malignant PVT (1-year-survival 193 vs. 2755 days; p < 0.001). Patients with nonmalignant PVT treated with long-term anticoagulation showed higher resolution/regression rates than non-malignant PVT patients without treatment (60% vs. 28%). Liver function also improved in these patients, in contrast to patients without anticoagulation (AST -10% vs. +20%; ALT -19% vs. +13%). The proportion of patients with ascites decreased with anticoagulation (-40%) and the mean serum albumin level increased (+19.6%) during follow-up. The proportion of patients with ascites did not significantly change without anticoagulation (+3%), neither changed the serum albumin levels during follow-up without anticoagulation (-0.1%). Conclusions: In this study there were no differences in survival between patients with or without anticoagulation. We found beneficial effects of anticoagulation in non-malignant PVT: Interestingly there was not only an improved regression rate of PVT but also an improvement of liver function with anticoagulation. Prospective studies are necessary to confirm and highlight these findings.