ObjectiveLaser tissue soldering using photothermal solders is a technology that facilitates rapid sealing using heat‐induced changes in the tissue and the solder material. The solder material is made of gold nanorods embedded in a protein matrix patch that can be placed over the tissue rupture site and heated with a laser. Although laser tissue soldering is an attractive approach for surgical repair, potential photothermal damage can limit the success of this approach. Development of predictive mathematical models of photothermal effects including cell death, can lead to more efficient approaches in laser‐based tissue repair.MethodsWe describe an experimental and modeling investigation into photothermal solder patches for sealing porcine and mouse cadaver intestine sections using near‐infrared laser irradiation. Spatiotemporal changes in temperature were determined at the surface as well as various depths below the patch. A mathematical model, based on the finite element method, predicts the spatiotemporal temperature distribution in the patch and surrounding tissue, as well as concomitant cell death in the tissue is described.ResultsFor both the porcine and mouse intestine systems, the model predicts temperatures that are quantitatively similar to the experimental measurements with the model predictions of temperature increase often being within a just a few degrees of experimental measurements.ConclusionThis mathematical model can be employed to identify optimal conditions for minimizing healthy cell death while still achieving a strong seal of the ruptured tissue using laser soldering. Lasers Surg. Med. 50:143–152, 2018. © 2017 Wiley Periodicals, Inc.