The safety and efficacy of a compound endoscopic dissection knife were evaluated in animal models. The compound endoscopic dissection knife can readily switch between Dual knife mode and IT knife mode. Vitro experiments were done on 30 mucosal lesion models and 30 submucosal lesion models, respectively, of pig stomach tissue. In vivo experiments, mucosal lesion resection were performed on each 10 lesions of gastrointestinal tract in 6 porcine models. The compound endoscopic dissection knife were used in the experimental group, and Dual knife combined with IT knife were used in the control group. Dissection time were recorded. The wounds were biopsied to evaluate muscle damage. The results of vitro experiment showed the dissection time of mucosal and submucosal lesions in the experiment group was significantly shorter than that in the control group (17.93±2.52 min VS 21.07±3.58 min, t=-2.774, P=0.010; 25.73±2.66 min VS 31.80±3.78 min, t=-5.081, P<0.001). The results of vivo experiment showed the dissection time in the experiment group was significantly shorter than that in the control group (21.67±4.10 min VS 25.36±3.83 min, t=-3.602, P=0.001). The muscle damage rate was lower in the experimental group, but the difference was not statistically significant [3.3% (1/30) VS 10.0% (3/30), χ²=1.071, P=0.612]. The compound endoscopic dissection knife is both safe and effective in animal models.