To evaluate the indication, approach, safety, and outcomes of percutaneous mesocaval shunt placement Institutional review board-approved retrospective review of the electronic medical records of patients with percutaneous mesocaval shunts was performed from January 2001 through March 2020 (n = 5). Indication for mesocaval shunt placement was refractory variceal hemorrhage in all 5 patients. All patients had extensive portal vein thrombosis (PVT) (1 intrahepatic, 4 extrahepatic) precluding transjugular intrahepatic portosystemic shunt placement. The underlying etiologies for PVT were non-alcoholic cirrhosis, primary sclerosing cholangitis, pancreatic cancer, post-surgical, and during pregnancy of indeterminate etiology. Post-procedurally, patients were followed for up to 10 years with clinical and laboratory assessment as well as CT or MRI imaging. Technical success was defined as placement of a stent from the superior mesenteric vein to the inferior vena cava. Clinical success was defined as cessation of refractory bleeding. Patient demographics, technical approach for placement, pre-procedure and post-procedure MELD scores, shunt patency, and complications were recorded. Technical and clinical success was achieved in 100% (5 of 5) of patients. Procedural imaging was available for 4/5 patients. To perform the inferior vena cava to superior mesenteric vein puncture, a combination of fluoroscopy and intravascular ultrasound was used in 25% (1/4), fluoroscopy and transabdominal ultrasonography was used in 25% (1/4), and fluoroscopy and intracardiac echocardiography was used in 50% (2/4). MELD scores (9 – 29) did not significantly deviate from pre-procedure to 30 days post-procedure in any patient. Mesocaval shunt primary unassisted patency was 5/5 (100%) at 6 months, 4/4 (100%) at 12 and 18 months, and 2/3 (67%) at 24 months. After 32 months, one patient underwent intentional mesocaval shunt closure for chronic, refractory hepatic encephalopathy (HE). The final patient maintained mesocaval shunt patency for greater than 10 years. No immediate complications occurred peri-procedurally. Two patients (40%) suffered HE, one of which resolved with medical optimization and the second required eventual shunt closure. Mesocaval shunt placement is an uncommonly performed procedure to treat complications of portal hypertension when a TIPS cannot be placed. In this cohort, outcomes were comparable to TIPS as it was safe, well tolerated, and remained patent in a majority of patients at 24 months.