The waterjet-assisted ESD technology (WESD) allows pressure controlled injection of fluids through the tip of a recently developed HybridKnife®. Submucosal injection, circumferential cutting and dissection of lesions as well as coagulation of bleeding sources can be performed with the same device without need for changing the instrument. These options should accelerate the procedure and may increase its safety and efficacy. Experimental trials in ex vivo and in vivo pig models showed that the gastrointestinal mucosa of different sites can be effectively and safely lifted by gentle placement of the HybridKnife® on the wall and needleless injection of saline solution with pressures between 30 - 70 bar. Our group reported on effective en-bloc resection of esophageal areas in all of 14 cases of an Erlangen porcine model. We subsequently compared WESD with EMR of predefined esophageal mucosal lesions in anesthetizised pigs in a randomized controlled trial. The results demonstrated that WESD more frequently achieved a complete resection with a significantly lower number of specimen. WESD caused no perforations and bleedings could be endoscopically managed during the procedure.