© 2014 Nova Science Publishers, Inc. All rights reserved. A non-surgical percutaneous interventional procedure known as transjugular intrahepatic portosystemic shunt (TIPS) was successfully applied in clinical practice just a little over two decades ago. In a relatively short period of time since its inception it has assumed a prominent role in the treatment of the complications of cirrhosis. While the incidence of classic etiologies of cirrhosis may have not changed significantly, the prevalence of non-traditional causes of cirrhosis is rising. The millions of people infected insidiously 3-4 decades ago with hepatitis C virus (HCV) are manifesting now, and many more suffering from the "metabolic syndrome" of obesity, diabetes and hypertension that can be connected to non-alcoholic fatty liver disease is increasing. These patients are presenting with HCV cirrhosis and non-alcoholic steato-hepatitis (NASH). The new cirrhotic patients will undoubtedly increase the demand for procedures required to treat the complications of their disease, mainly related to portal hypertension, such as endoscopic procedures, TIPS, hepatocellular carcinoma (HCC) therapies and liver transplants. Since its introduction as a second line treatment for variceal bleeding, the indications for TIPS have expanded to encompass other complications of liver disease, including refractory ascites, Budd-Chiari syndrome, hepatic hydrothorax, hepatorenal syndrome and portal gastropathy. We have performed over 900 TIPS in our institution over the past twenty years with considerable clinical success and rare technical failures or complications. In this chapter, we will describe our experience with TIPS and its role in the management of variceal upper gastrointestinal bleeding.