Introduction. There has been limited reporting on the use of hepatic-directed therapy in liver dominant hepatic metastases arising from pancreatic cancer. Methods. An IRB-approved prospective multi-institutional treatment registry of 885 patients undergoing 1458 treatments for primary or secondary cancers in the liver was evaluated from January 2007 to January 2011. Results. Ten patients underwent a total of 17 treatment sessions with drug-eluting beads (DEBs). Six patients received concurrent chemotherapy while undergoing DEB with no severe adverse events. After a median followup of 16 months, the 6- and 12-month response rates were 80% and 75%, respectively, with a median overall survival of 9.3 months. Conclusion. Hepatic arterial therapy with DEB can be safely and effectively used in selected patients with liver predominant metastatic disease from pancreatic cancer. This therapy should be considered in combination with systemic chemotherapy as a possible second therapy given the limited response rates of second-line chemotherapy.