Treatment of port wine stain (PWS) birthmarks in human skin by pulsed laser irradiation requires the knowledge of the maximum epidermal temperature rise and PWS depth for an attending physician to select the optimal light dosage, irradiation wavelength, and cryogen spray cooling spurt duration on an individual patient basis. Pulsed photothermal radiometry (PPTR) is a promising technique to provide such information. In this article, computer simulations are performed to evaluate the performance of PPTR depth profiling of the laser-induced temperature rise in PWS. An iterative, non-negatively constrained conjugate gradient algorithm is used to reconstruct the laser-induced temperature profile from simulated PPTR signals. Human skin is assumed to contain an epidermal melanin layer and a single homogeneous PWS layer in the dermis. The influence of structural, experimental, and algorithm parameters on the temperature profile reconstruction are discussed. Accuracy of the maximum epidermal temperature rise and PWS depth determined from the reconstructed profiles is statistically analyzed. The simulations show that when the melanin and PWS layers are physically discrete, a good reconstruction can be obtained and the maximum epidermal temperature rise and PWS depth can be determined with accuracy sufficient for the intended clinical application. Measurements and reconstructions from PWS patients are performed and the results are in agreement with the simulations.