Objective To explore the safety and efficiency of a novel bipolar electric knife for endoscopic submucosal dissection. Methods The thermal damage on tissue caused by the new bipolar knife and traditional monopolar knife were compared by finite element analysis. The vertical thermal damage to the porcine gastric wall caused by the two types of electric knife were analyzed in vitro animal experiments. In vivo animal experiments were used to compare operation related indexes of two types of electric knife, including en bloc resection rate and cutting efficiency in porcine digestive tract submucosal dissection. Results Through overcoming deviation of experimental individuals and operator experience, the finite element model showed that the length, width and depth of thermal damage on tissue caused by the monopolar knife was 1.08 times, 1.12 times, and 1.23 times of that of the bipolar knife, respectively. Additionally, the bipolar knife caused less vertical thermal damage to the porcine gastric wall than the monopolar knife (433.25±42.58 μm VS 898.03±111.59 μm, t=6.740, P=0.003) in vitro animal experiments when charged for 1 s at the same power. Finally, in vivo animal experiments showed that the en bloc resection rates of the two kinds of electric knife systems were both 100.0%. In addition, the cutting area and cutting time of the bipolar knife was 229.58±185.29 mm2 and 164.37±96.27 s, respectively. The corresponding indicators of the monopolar knife was 209.70±167.35 mm2 and 162.65±69.97 s, respectively, and there was no significant difference (all P>0.05). Conclusion The novel bipolar knife not only ensures the cutting efficiency but also reduces the thermal damage during endoscopic submucosal dissection in simulating experiment and animal experiment, which needs further verification in clinical trial.