PURPOSE: To compare the anatomic and clinical features in patients with chronic portal vein thrombosis (PVT) to determine why some patients develop portal biliopathy (PB) while most do not and propose an etiology for PB. MATERIALS AND METHODS: This project satisfied HIPAA regulations and received institutional review board approval for a retrospective review without the need for consent. From 100 patients with PVT, 60 were extracted who had chronic, nonmalignant PVT, after exclusion of those with sclerosing cholangitis, liver transplants, choledocholithiasis, or portosystemic shunts. Clinical and imaging data from 19 patients with biliary dilatation (PB group) were compared with data from 41 patients without biliary dilatation (no-PB group). Statistical analysis was performed with the Fisher exact test for categorical variables or the Wilcoxon rank-sum test for numerical and ordered categorical variables. P values of .05 or less were considered to indicate a significant difference. RESULTS: The etiology of PVT differed between the groups (P < .001); cirrhosis was infrequently seen in the PB group (two of 19, 11%) but was common in the no-PB group (31 of 41, 76%). Only two of 33 (6%) patients with cirrhosis and PVT had PB. Extension of PVT into the mesenteric veins was significantly more common in the PB group (18 of 19, 95%) than in the no-PB group (one of 41, 2%) (P < .001). Compared with the no-PB group, patients in the PB group had more acute angulation of the bile duct (median, 110° vs 128°; P = .008), less frequent gastroesophageal varices (three of 19 [16%] vs 20 of 41 [49%], P = .021), and a smaller mean coronary vein diameter (median, 5 vs 6 mm; P = .014). CONCLUSION: Noncirrhotic patients with hypercoagulable states tend to develop PB when PVT extends to the splenomesenteric veins. A possible etiology is the formation of specific peribiliary venous pathways responsible for bile duct compression and tethering.