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Background: For patients with small-size colorectal liver metastases, growing evidence suggests thermal ablation to be associated with fewer adverse events and faster recovery than resection while also challenging resection in terms of local control and overall survival. This study assessed the potential non-inferiority of thermal ablation compared with surgical resection in patients with small-size resectable colorectal liver metastases., Methods: Adult patients (aged ≥18 years) from 14 centres in the Netherlands, Belgium, and Italy with ten or fewer small-size (≤3 cm) colorectal liver metastases, no extrahepatic metastases, and an Eastern Cooperative Oncology Group performance status of 0-2, were stratified per centre, and according to their disease burden, into low, intermediate, and high disease burden subgroups and randomly assigned 1:1 to receive either thermal ablation (experimental group) or surgical resection (control group) of all target colorectal liver metastases using the web-based module Castor electronic data capture with variable block sizes of 4, 6, and 8. Although at the operator's discretion, a minimally invasive approach in both treatment groups was recommended. The primary endpoint was overall survival, assessed in the intention-to-treat population. A hazard ratio (HR) of 1·30 was considered the upper limit of non-inferiority for the primary endpoint. A preplanned interim analysis with predefined stopping rules for futility (conditional power to prove the null hypothesis <20%) and early benefit (conditional power >90%, superior safety outcomes for the experimental group, and no difference or superiority regarding local control for the experimental group) was done 12 months after enrolment of 50% of the planned sample size. Safety was assessed per treatment group. This trial is registered with ClinicalTrials.gov, NCT03088150., Findings: Between Aug 7, 2017, and Feb 14, 2024, 300 patients were randomly assigned to the experimental group (n=148, 100 male [68%] and 48 female [32%]; median age 67·9 years [IQR 29·2-85·7]) or to the control group (n=148, 107 male [72%] and 41 female [28%]; median age 65·1 [IQR 31·4-87·4]); four patients (two in each treatment group) were excluded after randomisation because they were found to have other disease pathology. Median follow-up at the prespecified interim analysis was 28·9 months (IQR 0·3-77·8). The trial was stopped early for meeting the predefined stopping rules: (1) a conditional likelihood to prove non-inferiority for overall survival of 90·5% (median overall survival not reached in both groups; HR 1·05; 95% CI 0·69-1·58; p=0·83), (2) a non-inferior local control (median local control not reached in both groups; HR 0·13, 95% CI 0·02-1·06; p=0·057), and (3) a superior safety profile for the experimental group. Patients in the experimental group had fewer adverse events than those in the control group (28 [19%] vs 67 [46%]; p<0·0001). Serious adverse events occurred in 11 (7%) of 148 patients in the experimental group and 29 (20%) of 146 in the control group, mostly periprocedural haemorrhage requiring intervention (one [1%] vs eight [5%]), and infectious complications requiring intervention (six [4%] vs 11 [8%]). There were no treatment-related deaths in the experimental group and three treatment-related deaths (2%) in the control group (two due to postoperative cardiac complications and one due to sepsis and liver failure)., Interpretation: The assumption that thermal ablation should be reserved for unresectable colorectal liver metastases requires re-evaluation and the preferred treatment should be individualised and based on clinical characteristics and available expertise., Funding: Medtronic-Covidien., Competing Interests: Declarations of interests MRM declares funding related to the present manuscript from Medtronic Covidien; receipt of institutional grants from Medtronic Covidien, Angiodynamics, Johnson&Johnson, and Immunophotonics, outside the submitted work; consulting fees from Angiodynamics, outside the submitted work; payment for lectures and presentations from Medtronic Covidien, Johnson&Johnson, and Philips Medical, outside the submitted work; travel grants from Angiodynamics, outside the submitted work. SvdL declares receipt of an institutional grant from Medtronic Covidien; and payment for lectures and presentations and travel support from AngioDynamics, outside of the submitted work. RSP declares receipt of grant from Terumo, Sirtex, AngioDynamics, MML-Medical, Sectra, Dutch Society for Interventional Radiologie; consulting fees from Medtronic Covidien; payment for lecture from Medtronic Covidien and AngioDynamics; support for attending meetings from AngioDynamics; and leadership or fiduciary role in other board from Dutch Society of Interventional Radiology, outside of the submitted work. HJS declares consulting fees and payment for lectures and presentation from AngioDynamics; and support for attending meetings from CIRSE and Spectrum conference, outside of the submitted work. MCB declares receipt of institutional grant from Innovative Health Initiative–EU HORIZON and KWF (Dutch Cancer Society); payment for lectures and presentations from Philips and RIDN; participation on a DSMB for PLASTICS-3 and Dutch Liver Patient Organization Advisory Board; and leadership or fiduciary role in Dutch Benign Liver Tumor Group and Scientific Committee Dutch Society of Interventional Radiology, outside of the submitted work. CGO declares receipt of institutional grants from Siemens Healthineers, outside of the submitted work. MLJS declares payment for lectures and presentations from Medtronic Covidien, Teruma, and Philips to institution, outside of the submitted work; and Chair of Scientific Committee of Dutch Interventional Radiology Society (unpaid). CvdL declares receipt of institutional IHI Horizon Grant from IMAGIO wp3. BG declares receipt of institutional grant from AngioDynamics, Prins Bernhard Culuur Fonds, and Nijbakker Morra Stichting; and financial support for PhD thesis from AngioDynamics, outside of the submitted work. MB declares receipt of institutional grants from Intuitive, Medtronic Covidien, Oncosil and Ethicon, outside of the submitted work. JH declares payment for proctoring from Intuitive Surgical, outside of the submitted work. RJS declares payment for proctoring from Intuitive Surgical, outside of the submitted work. RMvD declares receipt of an institutional grant from KWF, ZonMw, National Institute for Health and Care Research, Canadian Institutes of Health Research, Abbot, and Guerbet, outside of the submitted work. TEB declares payment for lectures and presentations from Pierre Fabre; and advisory board BMS, outside of the submitted work. TC declares consulting fees from Cascination, outside of the submitted work. All other authors declared no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)