Polycystic liver disease (PCLD) has long been considered to represent a contraindication to transjugular intrahepatic portosystemic shunt (TIPS) creation, primarily because of the risk of hemorrhage. Three-dimensional (3D) navigation within the enlarged and potentially disorienting parenchyma can now be performed during the procedure with the development of C-arm cone-beam computed tomography, which relies on the same equipment already used for angiography. Such a hybrid 3D reconstruction-enabled angiography system was used for safe image guidance of a TIPS procedure in a patient with PCLD. This technology has the potential to expedite any image-guided procedure that requires 3D navigation.