BACKGROUND: The development of the EndoMaster "Endoluminal Access Surgical Efficacy" (EASE) system aims to enhance the safety and efficacy of colonic endoscopic submucosal dissection (ESD) through two flexible robotic arms. This is the first clinical trial to evaluate the performance of colorectal ESD using EndoMaster. METHOD: Patients with early mucosal colorectal neoplasia that was not suitable for en bloc resection with snare-based techniques were recruited. The EndoMaster EASE robotic system consisted of an independently designed flexible robotic platform with two robotic arms. The primary outcome was the complete resection rate using EndoMaster. Secondary outcomes included operating time, hospital stay, procedure-related complications, and oncologic outcomes. RESULTS: 43 patients underwent robotic ESD, with a median robotic dissection time of 49 minutes. The technical success rate was 86.0%, while en bloc resection rate among cases with technical success was 94.6%. The complete resection rate was 83.8% and the median size of specimen was 35 mm (range 15-90 mm). The median hospital stay was 2 (range 1-7) days and there was one delayed bleed after 4 days, which was controlled endoscopically. One patient sustained perforation during the procedure, which was completely closed using clips without sequelae. Two patients were treated by salvage surgery. CONCLUSION: This first clinical trial confirmed the safety and efficacy of performing colorectal ESD using the EndoMaster EASE robotic system.