OBJECTIVES: Combined Budd-Chiari syndrome and Portal Vein Thrombosis (BCS-PVT) is a challenging clinical condition with as yet unknown outcome. The aim of the present study was to investigate etiology, treatment options, and prognosis of patients with BCS-PVT. METHODS: Patients diagnosed with nonmalignant BCS between 1984 and 2001 were identified in a large international study and classified into isolated BCS (n = 204), BCS-PVT without spleno-mesenteric vein thrombosis (SMVT; n = 15), and BCS-PVT with SMVT (n = 18). RESULTS: Multifactorial etiology was present in 58% of patients with combined BCS-PVT. Number of etiological factors increased significantly with the extent of thrombosis (p= 0.002). Main treatment options included anticoagulation and portosystemic shunting, of which extended TIPS showed the most beneficial results. Five-year survival was 59% (95% CI 39-80%) in BCS-PVT versus 85% (95% CI 76-88%) in isolated BCS (p= 0.11). Survival tended to be worse in BCS-PVT patients with SMVT as compared to patients without SMVT (RR = 3.47, p= 0.11). CONCLUSIONS: In BCS, extension of thrombosis into the splanchnic venous bed was significantly related to the number of etiological factors, and was associated with poor outcome. These results strongly support a liberal use of anticoagulants, which so far had been widely debated. Alternatively, derivative shunt procedures appear difficult, yet not impossible.