During laser-assisted photo-thermal therapy, the temperature of the heated tissue region must rise to the therapeutic value (e.g., 43°C) for complete ablation of the target cells. Large blood vessels (larger than 500 micron in diameter) at or near the irradiated tissues have a considerable impact on the transient temperature distribution in the tissue. In this study, the cooling effects of large blood vessels on temperature distribution in tissues during laser irradiation are predicted using finite element based simulation. A uniform flow is assumed at the entrance and three-dimensional conjugate heat transfer equations in the tissue region and the blood region are simultaneously solved for different vascular models. A volumetric heat source term based on Beer-Lambert law is introduced into the energy equation to account for laser heating. The heating pattern is taken to depend on the absorption and scattering coefficients of the tissue medium. Experiments are also conducted on tissue mimics in the presence and absence of simulated blood vessels to validate the numerical model. The coupled heat transfer between thermally significant blood vessels and their surrounding tissue for three different tissue-vascular networks are analyzed keeping the laser irradiation constant. A surface temperature map is obtained for different vascular models and for the bare tissue (without blood vessels). The transient temperature distribution is seen to differ according to the nature of the vascular network, blood vessel size, flow rate, laser spot size, laser power and tissue blood perfusion rate. The simulations suggest that the blood flow through large blood vessels in the vicinity of the photothermally heated tissue can lead to inefficient heating of the target.