Port wine stains (PWSs) are congenital dermal vessel proliferations mainly treated with laser therapy. The complete removal of the vessel lesions is rarely achieved because of a lack of discriminatory analysis of the two competitive laser damages to blood vessels, namely, pressure damage and thermal damage. Unlike complete vessel constriction, which is caused by thermal damage that can be measured by temperature-related integral Ω, vessel rupture results from pressure damage, which has been seldom studied. In this study, the rupture potential index based on wall pressure (RPIP) was calculated as the ratio of locally acting pressure to the pressure threshold. RPIP > 1 and Ω > 103 were adopted as benchmarks to judge pressure damage (vessel rupture) and thermal damage (complete vessel constriction), respectively. A computational fluid dynamics simulation was carried out to provide the temperature and pressure field in the PWS vessel model during irradiation by 595 nm pulsed dye laser (PDL) or 1064 nm Nd:YAG laser. Numerical results showed that for the 595 nm laser, vessels constantly underwent rupture. The area of high RPIP determined the degree of rupture by predicting the large and multiple rupture locations of the vessel. By contrast, for the 1064 nm laser, complete constriction was the main damage type. To a single vessel of 100 μm diameter, the optimized laser parameters were E = 10 J/cm2 with tp = 6 ms for 595 nm PDL and E = 180 J/cm2 with tp = 6 ms 1064 nm for Nd:YAG laser.