| Summary: | Radiofrequency ablation (RFA) is a curative treatment for early-stage hepatocellular carcinoma (HCC) ineligible for surgery or liver transplantation. However, trans-arterial chemoembolization (TACE) might be an alternative when RFA is contraindicated due to structural problems. Here, we aimed to compare their long-term outcomes. Treatment-naive HCC patients fulfilling the Milan criteria who underwent RFA (<i>n</i> = 136) or TACE (<i>n</i> = 268) were enrolled. Complete response (CR) and 5-year recurrence-free survival (RFS) rates were higher in the RFA group than in the TACE group (94.1% vs. 71.6% and 35.8% vs. 17.0%, respectively; both <i>p</i> < 0.001), whereas 5-year overall survival (OS) rates were not significantly different (65.5% vs. 72.3%, respectively; <i>p</i> = 0.100). Multivariate analysis showed that RFA was associated with better RFS (adjusted hazard ratio [aHR] 0.628; <i>p</i> = 0.001) than TACE, but not with better OS (aHR 1.325; <i>p</i> = 0.151). The most common 1st-line treatment after recurrence were TACE (<i>n</i> = 53), followed by RFA (<i>n</i> = 21) among the RFA group and TACE (<i>n</i> = 150), followed by RFA (<i>n</i> = 44) among the TACE group. After propensity-score matching, similar results were reproduced. Hence, TACE could be an effective alternative to RFA in terms of OS rates. However, TACE should be confined only to RFA-difficult cases, given its lower CR and RFS rates and multi-disciplinary approaches are desirable in decision-making.
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