Objectives <p>At present, there are no established clinical guidelines for radiofrequency ablation (RFA) of peribiliary hepatocellular carcinoma (HCC). Therefore, the aim of this study was to compare the long-term outcomes of RFA for peribiliary vs. non-peribiliary HCC.</p> Methods <p>This retrospective study included 282 patients with peribiliary HCC (<i>n</i> = 109) or non-peribiliary HCC (<i>n</i> = 173) who received RFA between February 2013 and May 2021. Local tumor progression (LTP), overall survival (OS), disease-free survival (DFS), and complications were compared before and after propensity score matching (PSM).</p> Results <p>Before PSM, there were no significant differences in 5-year LTP rates (26.3% vs. 23.6%, <i>p</i> = 0.602), OS rates (56.6% vs. 68.0%, <i>p</i> = 0.586), or DFS rates (22.9% vs. 25.7%, <i>p</i> = 0.239) between the peribiliary and non-peribiliary groups. After PSM, there were no significant differences in the 1-, 3-, and 5-year LTP rates (13.0%, 23.1%, and 26.3% vs. 12.1%, 25.1%, and 28.2%, respectively, <i>p</i> = 0.857), OS rates (97.2%, 73.5%, and 56.6% vs. 95.3%, 79.5%, and 70.6%, <i>p</i> = 0.727), or DFS rates (59.4%, 29.4%, and 22.9% vs. 64.2%, 33.1%, and 23.8%, <i>p</i> = 0.568) between the peribiliary non-peribiliary groups. Peribiliary location was not a significant prognostic factor for LTP (<i>p</i> = 0.622) or OS (<i>p</i> = 0.587). In addition, mild intrahepatic bile duct dilatation was more frequent in the peribiliary group (9.2% vs. 2.8%, <i>p</i> = 0.045).</p> Conclusion <p>Long-term outcomes of RFA were similar for peribiliary and non-peribiliary HCC. RFA is a viable alternative for treatment of peribiliary HCC.</p> Critical relevance statement <p>The local tumor progression (LTP), overall survival (OS), and disease-free survival (DFS) rates after radiofrequency ablation (RFA) were similar for peribiliary and non-peribiliary hepatocellular carcinoma (HCC).</p> Key Points <p><UnorderedList Mark="Bullet"> <ItemContent> <p>There are currently no clinical guidelines for radiofrequency ablation (RFA) of peribiliary hepatocellular carcinoma (HCC).</p> </ItemContent> <ItemContent> <p>Local tumor progression, overall survival, and disease-free survival after RFA were similar for peribiliary and non-peribiliary HCC.</p> </ItemContent> <ItemContent> <p>RFA is a viable alternative for the treatment of peribiliary HCC.</p> </ItemContent> </UnorderedList></p> Graphical Abstract <p></p>