OBJECTIVES: This study aimed to assess the efficacy and safety of radiofrequency ablation (RFA) for multifocal papillary thyroid carcinoma (M-PTC) and compare these outcomes with those for unifocal papillary thyroid carcinoma (U-PTC). METHODS: This retrospective multicenter study included 465 patients (367 women and 98 men) who underwent RFA for either U-PTC (411 patients) or M-PTC (54 patients) between May 2015 and October 2022. Patients were followed up at 1, 3, 6, and 12 months post-RFA, then every 6 months in the second year, and annually thereafter. After 1:1 propensity score matching (PSM), local tumor progression rate (LTP), tumor volume, volume reduction rate (VRR), tumor complete response rate (CDR), and complications were evaluated and compared between the M-PTC and U-PTC groups during the follow-up period. RESULTS: The median follow-up time was 23 months. The median follow-up time for the U-PTC and M-PTC groups was 23 months and 23.5 months, respectively. The overall local tumor progression rate was 0.9% (4/465), and the overall complication rate was 0.6% (3/465). After PSM, no significant differences were observed between the U-PTC and M-PTC groups regarding tumor volume ( CONCLUSION: After adequate preoperative evaluation, RFA is an effective and safe treatment for appropriately selected patients with M-PTC, with a prognosis similar to that of U-PTC.