Port wine stain (PWS) is a congenital, progressive vascular malformation of human skin. Presently, all PWS patients are treated using single cryogen spurt and single laser pulse exposure (SCS-SLP), which does not produce complete lesion blanching in the vast majority of patients. In this study, the feasibility of applying multiple cryogen spurts intermittently with multiple laser pulse exposures (MCS-MLP) is studied numerically. Laser therapy of PWS was simulated with finite element heat diffusion and Monte Carlo light distribution models. Epidermal and thermal damage of PWS blood vessels of various diameters (50130 m) were calculated with an Arrhenius-type kinetic model. The results show that the proposed MCS-MLP approach can provide sufficient epidermal protection while at the same time achieving higher core intravascular temperatures over longer periods of time. PWS patients may benefit from the MCS-MLP approach, depending on PWS vessels diameter.