An in vitro study of laser tissue welding mediated with a dye-enhanced protein solder was performed. Freshly harvested sections of porcine aorta were used for the experiments. Arteriotomies approximately 4 mm in length were treated using an 805 nm continuous-wave diode laser coupled to a 1-mm diameter fiber. Temperature histories of the surface of the weld site were obtained using a fiberoptic-based infrared thermometer. The experimental effort was complemented by the LATIS (LAser-TISsue) computer code, which numerically simulates the exposure of tissue to near-infrared radiation using coupled Monte Carlo, thermal transport, and mass transport models. Comparison of the experimental and simulated thermal results shows that the inclusion of water transport and evaporative losses in the model is necessary to determine the thermal distributions and hydration state in the tissue. The hydration state of the weld site was correlated with the acute weld strength.