Intra-arterial radioembolization with yttrium-90 microspheres is a safe and effective treatment option for patients with unresectable liver tumors. Pretreatment coil embolization of extrahepatic vessels is recommended to avoid extrahepatic deposition of radioactive microspheres. A novel infusion system with an expandable tip, the Surefire Infusion System (SIS), has recently been developed to minimize reflux. We report three cases of radioembolization with the use of the SIS. In all cases, yttrium-90 radioembolization was performed successfully without coil embolization of extrahepatic vessels. In all patients, positron emission tomography-computed tomography confirmed intrahepatic biodistribution of the microspheres in all targeted liver segments, and no extrahepatic deposition. With the use of the SIS, the need for coil embolization of extrahepatic vessels might be eliminated, and treatment may be extended to patients who were previously deemed unfit.