More data about TACE and pTACE seem necessary to better define the global treatment strategy for HCC. Aim of our analysis was to evaluate the role of TACE, either with lipiodol (traditional) or drug-eluting microspheres in terms of response rate (RR), time to progression (TTP), overall survival (OS) and toxicity in HCC. Patients with HCC undergoing traditional TACE or pTACE (either alone or in combination with other treatment options) were eligible One hundred and fifty patients were analyzed. In the global patient population median OS was 46 months for lipiodol TACE and 19 months for pTACE (p less than 0.0001), TTP was 30 months versus 16 months for patients receiving TACE or pTACE respectively (p = 0.003). These results were confirmed also among the group of patients who received exclusive TACE or pTACE. Neither RR nor toxicity was different between TACE or pTACE. At multivariate analysis, age, the Okuda stage, type of TACE and number of TACE proved to be independent prognostic factors influencing overall survival. In our experience, lipiodol TACE showed a better OS and TTP over pTACE, without difference in toxicity profile and RR. Among the staging systems analyzed only the Okuda stage seemed able to reliably predict patients outcome.