Port wine stain (PWS) birthmarks are progressive vascular malformations that occur in ∼12,000 live births per year in the United States. The majority (∼90%) of PWS birthmarks occur on the head and neck regions, and thus are difficult to conceal. The psychosocial development of individuals with PWS birthmarks is adversely affected. Facial PWS lesions have been associated with increased incidence of glaucoma and seizures. The progressive nature of PWS skin may be due to lack of neuronal regulation of blood vessel size. Progressive development of the PWS results in a darker appearance, soft tissue hypertrophy, nodularity, and overall further disfigurement. Current treatment options have significant limitations in terms of efficacy and risk. With laser therapy, a reduction in size and degree of redness of PWS skin occurs in ∼60% of treated patients. After ten treatment sessions, complete disappearance of the PWS occurs in only ∼10% of treated patients. To reduce the financial burden and potential risks of repeated treatments under general anesthesia, there is a need for innovative, personalized methods to maximize the reduction in PWS redness per treatment session. Without addressing this need, the overall efficacy of PWS laser therapy will remain variable, because treatment protocols will remain based primarily on the subjective impression and overall experience of the treating surgeon. To address this need, we propose use of laser speckle imaging (LSI) to provide real-time, quantitative feedback during laser surgery.