Background/Aims:To compare the efficacy and safety profile of doxorubicin-loaded drug-eluting beads (DEB) to the conventional TACE (C-TACE) in the management of nonresectable hepatocellular carcinoma (HCC).Patients and Methods:All patients with nonresectable HCC who underwent either c-TACE or DEB-TACE during the period 2006–2014 and fulfilled the inclusion criteria were included in this retrospective study. Primary endpoints were tumor response rate at first imaging follow up, treatment-related liver toxicity, and treatment emergent adverse events (TEAE).Results:Thirty-five patients (51 procedures) in the DEB-TACE group and 19 patients (25 procedures) in the c-TACE group were included in the analysis. The median follow up time was 61 days (range 24–538 days) in the DEB-TACE group and 86 days (range 3–152 days) for the c-TACE group patients. Complete response (CR), objective response (OR), disease control (DC), and progressive disease (PD) rates were 11%, 24%, 53%, and 47%, respectively, in the DEB = TACE group compared with 4%, 32%, 64%, and 36%, respectively, in the c-TACE group. Mean ALT change from baseline was minimal in the DEB-TACE patients compared with c-TACE group (7.2 vs 79.4 units, P = 0.001). Hospital stay was significantly shorter in the DEB-TACE group (7.8 days vs 11.4 days; P = 0.038). The 2-year survival rate was 60% for the c-TACE patients and 58% for the DEB-TACE (P = 0.4).Conclusions:DEB-TACE compared with c-TACE is associated with lesser liver toxicity benefit, better tolerance, and shorter hospital stay. The two modalities however had similar survival and efficacy benefits.