Background and Objectives: The objective of this study was to compare the efficacy and safety of cryogen spray cooled laser treatment (CSC-LT) at wavelengths of 585 nm vs. 595 nm for port wine stain (PWS) birthmarks in a large series of patients. Study Design/Materials and Methods: A retrospective review was conducted of 64 patients with PWS treated with the ScleroPLUS 1 [Candela (Wayland, MA)] pulsed dye laser (l ¼ 585 or 595 nm wavelength; spot size 7 mm, t p ¼ 1,500 microseconds) over a 3-year period. Subjects' ages ranged between 3 months and 64 years; there were 42 females and 22 males, all of whom were Asian. Number of treatments ranged from 1 to 6. Duration of treatment ranged from 6 months to 2 years 11 months, with a mean of 12 months. Patients (n ¼ 32) received CSC-LT (585 nm) using radiant exposures of 7-10 J/cm 2 . A second group of patients (n ¼ 32) received CSC-LT (595 nm) using radiant exposures of 7-10 J/cm 2 . The primary efficacy measurement was the quantitative assessment of blanching response scores for CSC-LT (585 nm) versus CSC-LT (595 nm). Patients were monitored for adverse effects. Results: Based on chi-squared analysis, there were clinical, and statistically significant, differences in blanching response scores favoring PWS receiving CSC-LT (585 nm) as compared to CSC-LT (595 nm) (P < .001). Transient hyperpigmentation was noted in 43.7% (n ¼ 14) and 37.5% (n ¼ 12) of patients in the CSC-LT (585 nm) and CSC-LT (595 nm) groups, respectively. In both groups, transient hyperpigmentation resolved in all patients within 1 year. Permanent hypopigmentation or scarring was not observed in either group. Conclusions: CSC-LT (585 nm) resulted in superior blanching as compared to CSC-LT (595 nm). Further study is required to optimize wavelength selection on an individual patient basis during PWS therapy in order to improve treatment results.