To describe survival data of elderly patients with hepatocellular carcinoma (HCC) treated with loco-regional therapy (LRT) and to compare the survival outcomes of “transplantable” LRT patients with patients with HCC outside the criteria for liver transplantation (LT). We retrospectively reviewed the clinical and tumor information of 743 consecutive patients older than 65 years at time of HCC diagnosis treated with LRT from 1998 to 2018 at a single center. This study included only patients with HCC and a known diagnosis date and excluded patients treated surgically prior to LRT or eventually underwent LT. The primary endpoint was overall survival. To establish Milan criteria status, each patient was assessed for size and number of tumors at diagnosis. Patients included in this study, both within and outside Milan criteria radiologically, were ultimately not transplant candidates due to a variety of clinical and social reasons. Results were analyzed using a Kaplan-Meier method and a univariate Cox regression model. Two hundred and eighty-five patients met the inclusion criteria (age 72.5 ± 5.6). The 1, 3, and 5-year overall survival for the total cohort was 70.7%, 34.8%, and 23.2%. One hundred and fifty-five (54%) patients were within Milan criteria, 98(34%) were not, and 33 were unknown. There were no significant differences in age at first procedure between the two groups (P = 0.8464). The 1, 3, and 5-year overall survival after LRT for patients within Milan versus outside Milan criteria were 77.9% versus 62.0%, 43.7% versus 23.3%, and 35.4% versus 8.75%, respectively (P <0.001, hazards ratio: 1.93, 95% confidence interval [1.37-2.71]). Liver transplantation remains the best therapeutic option for elderly patients with HCC that can be transplanted. For patients that are not transplant candidates, LRT is a viable alternative. As expected, overall survival rate is heavily impacted by stage of initial disease, further research is needed to identify and develop better therapeutic strategies for patients with advanced disease.Tabled 1GroupAge1-Year OS (95% CI)3-Year OS (95% CI)5-Year OS (95% CI)Within Milan72.2 ± 5.977.9% (71.3%-85.1%)43.7% (35.4%-54.1%)35.4% (26.2%-47.8%)Outside Milan72.4 ± 5.063.3% (54.0%-74.2%)23.3% (14.4%-37.8%)8.75% (3.17%-24.2%) Open table in a new tab