4598 Background: Level 1A of evidence proves that TACE may prolong survival in HCC patients, for whom potentially curative treatment is no longer possible. DEB-TACE is a drug delivery system comprised of micrometer-sized polyvinyl alcohol hydrogel particles preloaded with doxorubicin, combining vascular embolization with intratumoral drug release. Methods: Among other major inclusion criteria, pathological diagnosis of HCC, uneligibility from curative options, age >18 yrs, and adequate liver/hematological function were all required. DEB were selectively infused into the hepatic artery, or superselectively instilled into a few of its minor branches to block the blood flow while slowly discharging the drug. Patients were treated with doxorubicin dose adjustment for bilirubin values and BSA. Responses were evaluated accordingly to modified EASL criteria. Toxicities were registered using NCI-CTC criteria. Results: Over 28 months, we treated 158 liver lesions in 71 consecutive Child A/B, ECOG PS 0–1 HCC patients, who had previously failed other local procedures. Median age at the time of treatment was 69 years. Median diameter of the predominant lesion and median tumor load were 30 and 43 mm, respectively. Median dose of delivered doxorubicin was 60 mg (range 50–100). Radiological confirmed response rate was 94.2%. Among complete responders (74%), 77% and 67% had no further evidence of disease after a median follow-up of 6 and 12 months, respectively. The persistence of arterial enhancement (vascularization) in the treated area predicted hepatic recurrence (p=0.03). Postprocedural mild nausea, fever and local pain were frequently reported, but no myelotoxicity was registered. Although 30-days mortality rate was limited to 4%, prolonged hospitalization was needed in 5 cases: 1 severe abdominal pain, 2 hemorrhagic duodenitis, and 2 progressive hepatic failures. After complete response, two patients were reconsidered for curative procedures and finally underwent orthotopic liver transplantation. Conclusions: DEB-TACE is highly active, reasonably safe, and represents a feasible opportunity to achieve prolonged disease control in pretreated HCC patients. Occasionally, it may be considered as a bridge to liver transplantation. No significant financial relationships to disclose.