BACKGROUND: Transarterial chemoembolization (TACE) is a potential conversion therapeutic strategy for unresectable hepatocellular carcinoma (uHCC). However, therapeutic options following conversion therapy are still controversial. OBJECTIVES: This study aimed to compare the efficacy and safety of surgical resection (SR) and microwave ablation (MWA) after TACE conversion therapy for uHCC. DESIGN: A retrospective, multi-institutional study. METHODS: From June 2008 to October 2022, 8842 consecutive uHCC patients underwent initial TACE at 15 hospitals were identified. Among them, 1348 eligible patients who received TACE conversion therapy were included. The propensity score matching (PSM) was applied to reduce selection bias. To explore the effect of age on conversion therapy, a therapeutic factor analysis with age change was performed. The overall survival (OS) and disease-free survival (DFS) were compared using the Kaplan-Meier method with the log-rank test. RESULTS: After PSM 1:1, 542 patients in the MWA group were matched with those in the SR group. SR demonstrated better long-term survival outcomes (median OS, 10.6 vs 5.8 years, HR:1.83, 95% CI: 1.48-2.25, CONCLUSION: MWA might be acceptable as an alternative to SR in first-line therapeutic scheme after TACE conversion therapy for uHCC, especially, for the aged <
45 years cohorts.