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Endoscopic submucosal dissection (ESD) enables en bloc resection for early gastrointestinal malignancies but is technically challenging. A novel, endoluminal robotic platform was developed to address these limitations. We conducted a randomised, crossover study comparing conventional to robot-assisted ESD using an open ex-vivo bovine colon model. 10 endoscopists without ESD or robotic experience were randomised to perform either approach first. Robot-assisted ESD achieved a greater en bloc resection rate (100% vs 40%; p=0.011), shorter procedure times (32.3 vs 85.1 min; p<0.001), fewer muscle injuries, perforations and lower physical and mental workload compared with conventional ESD. Robot-assisted ESD may facilitate broader ESD adoption but requires further steps of assessment.