Objectives The transfer and widespread acceptance of laser-induced thermal therapy into gastroenterology remain a topic of interest. However, a practical approach to the quantitative effect of photothermal injury in the esophagus needs further investigation. Here, we aim to perform computer simulations that simulate laser scanning and calculate the laser-induced thermal damage area. The simulation engine offers the results in a guide map for laser coagulation with a well-confined therapeutic area according to laser irradiance and surface scanning speed. The study also presents validation experiments that include histology analyses in an ex vivo sheep esophagus model. Methods The simulation engine was developed based on the Monte-Carlo method and the Arrhenius damage integral. The computational model mimicked laser scanning by shifting the position of the calculated heat source in the grating system along the axis to be scanned. The performance of the simulations was tested in an ex vivo sheep esophagus model at a laser wavelength of 1505 nm. Histological analysis, hematoxylin-eosin staining, light microscope imaging, and block-face scanning electron microscopy were used to assess thermal damage to the tissue model. Results The developed simulation engine estimated the photothermal coagulation area for a surface scanning speed range of 0.5-8 mm/second and laser power of up to 0.5 W at a 0.9-nm laser diameter in a tissue model with a volume of 4 x 4 x 4 mm(3). For example, the optimum laser irradiation for effective photothermal coagulation in the mucosa and superficial submucosa depths was estimated to be between 16.4 and 31.8 W/cm(2), 23.2 and 38.1 W/cm(2) at 0.5 and 1 mm/second, respectively. The computational results, summarized as a guide map, were directly compared with the results of ex vivo tissue experiments. In addition, it was pointed out that the comparative theoretical and experimental data overlap significantly in terms of energy density. Conclusions Our results suggest that the developed simulation approach could be a seed algorithm for further preclinical and clinical trials and a complementary tool to the laser-induced photothermal coagulation technique for superficial treatments in the gastrointestinal tract. In future preclinical studies, it is thought that the simulation engine can be enriched by combining it with an in vivo model for different laser wavelengths.