Background and Objectives: Quantitative methods to assess port wine stain (PWS) skin response to laser therapy are needed to improve therapeutic outcome. In this study, PWS skin erythema was analyzed using erythema index difference (ΔEI: erythema index difference between PWS and normal skin) images before and after treatment to investigate systematically subject-dependent response to laser therapy. Study Design/Materials and Methods: Cross-polarized digital skin color images were acquired from 17 subjects with facial PWS and the associated ΔEI images were computed. Qualitative and quantitative analyses of PWS skin erythema were performed with ΔEI images, in which ranges of 40-6 and 5-0 represented PWS and normal skin, respectively. Results: After laser therapy, we qualitatively observed α reduction in the ΔEI values for all subjects. Regression fitting of ΔEI values before and after PWS laser therapy was associated with strong positive linear correlation. Conclusions: The imaging modality and analysis method allowed systematic analysis of PWS skin erythema in response to laser therapy. PWS skin response was dependent on pretreatment ΔEI values, suggesting that erythema can be utilized as an effective parameter to monitor PWS response to laser therapy. © 2005 Wiley-Liss, Inc.