<p>There is a lack of clinical consensus on the parameter settings of the pulsed-wave thulium fiber laser for soft tissue resection. The aim of this study was to explore the optimal parameter settings of the pulsed-wave thulium fiber laser for soft tissue resection, with a view to providing a reference for future clinical applications. Two different thulium fiber lasers, prototype thulium fiber lasers and Urolase, were used to explore the optimal parameters of thulium fiber laser for soft tissue cutting by evaluating the depth of tissue vaporization and depth of thermal damage in an isolated pig kidney model, and then the optimal parameters of in vitro screening were statistically validated by operation time, coagulation time, intraoperative hemorrhage, smoke level, and depth of thermal damage in an in vivo model using rabbit kidney. In ex vivo animal experiments the depth of tissue vaporization and thermal damage increased with increasing average power, and tissue carbonization occurred at 30&#xa0;W. In animal use we used 1&#xa0;J, 25&#xa0;W for surgery, and there was no statistical difference between the two thulium fiber lasers in terms of surgery time, coagulation time, bleeding, smoke level, and depth of thermal damage. Thulium fiber laser for soft tissue resection is safe and feasible, and we believe that 1&#xa0;J, 25&#xa0;W is the optimal laser setting parameter for soft tissue resection, but it needs to be adjusted according to the actual situation.</p> Graphical Abstract <p></p>