Cirrhosis with complications of portal hypertension portends a poor prognosis. Transjugular intrahepatic portosystemic shunts (TIPS) can successfully treat some of these complications in select patients. While the safety and efficacy of TIPS have improved significantly over the past decade, certain patients are categorized as high-risk based on various demographic, laboratory, and comorbid factors. Herein, we provide an in-depth review of TIPS in these settings, including high model for end-stage liver disease score, hepatic malignancy, advanced age, cardiac disease, renal dysfunction, and pregnancy, and discuss their impact on patient selection and procedural considerations.