A quantitative analysis method of CO2 laser treatments promotes laser treatment performance and rapid clinical application of novel treatment devices. The in silico clinical trial approach, which is based on computational simulation of light-tissue interactions using the mathematical model, can provide quantitative data. Although several simulation methods of laser tissue vaporization with CO2 laser treatments have been proposed, validations of the CO2 laser wavelength have been insu±cient. In this study, we demonstrated a tissue vaporization simulation using a CO2 laser and performed the experimental validation using a hydrogel phantom with constant physical parameters to evaluate the simulation accuracy of the vaporization process. The laser tissue vaporization simulation consists of the calculation of light transport, photothermal conversion, thermal diffusion, and phase change in the tissue. The vaporization width, depth, and area with CO2 laser irradiation to a tissue model were simulated. The simulated results differed from the actual vaporization width and depth by approximately 20% and 30%, respectively, because of the solubilization of the hydrogel phantom. Alternatively, the simulation vaporization area for all light irradiation parameters, which is related to the vaporization amount, agreed well with the actual vaporization values. These results suggest that the computational simulation can be used to evaluate the amount of tissue vaporization in the safety and effectiveness analysis of CO2 laser treatments.