Background: We conducted a multicenter prospective study (SURF trial) to compare the efficacy of surgery vs. radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC). SURF trial consisted of a randomized controlled trial (SURF-RCT) and a non-randomized prospective observational study (SURF-Cohort), including patients who did not consent to randomization. The initial report of the SURF-Cohort trial showed that recurrence-free survival (RFS) did not differ significantly between patients undergoing surgery and RFA. The focus of the present report was to assess the efficacy for overall survival (OS). Methods: The SURF-Cohort trial was a prospective multicenter study conducted in 49 institutions in Japan. Patients (aged between 29 and 79 years) with Child-Pugh scores ≤ 7, largest HCC diameter ≤ 3 cm, and ≤ 3 HCC nodules were considered eligible. Before the enrollment, both liver surgeons and hepatologists who perform RFA confirm that all the patients can be treated using both surgery and RFA. The co-primary endpoints were RFS and OS. OS was assessed at 5 years after the last accrual as per the protocol. Inverse probability of treatment weighted (IPTW) analysis was used to balance the characteristics of the groups. This trial is registered in UMIN000001796. Results: During 2009–2015, 782 patients were enrolled. After excluding ineligible patients, the surgery and RFA groups included 382 and 371 patients, respectively. In the surgery group, median platelet count (13.7x10⁴ vs. 11.5x10⁴, P< 0.01) was significantly greater, and the median largest HCC diameter was significantly greater (2.0 cm vs. 1.8 cm, P< 0.01) than in the RFA group. The median (range) follow-up period was 6.8 years in the surgery group and 6.7 years in the RFA group. The IPTW-adjusted OS did not differ significantly between the surgery and RFA groups: the 5-year OS, 79.7% vs. 79.3%; HR 0.98; 95% CI 0.75–1.30; P= 0.906. The analysis after long-term follow-up in the current report showed that RFS was not significantly different between the surgery and RFA groups: the 5-year RFS, 44.6% vs. 39.3%; HR 0.86; 95% CI 0.71–1.06; P= 0.155. Conclusions: SURF-Cohort trial revealed that OS and RFS after the IPTW adjustment were not significantly different between patients undergoing surgery and RFA for early stage HCC (≤ 3 cm and 3 nodules). Clinical trial information: UMIN000001796.