The blanching of resistant port wine stains (PWS) with a pulsed dye laser (PDL) requires a large number of treatments, resulting in substantial discomfort to patients, many of them children. Pneumatic skin flattening (PSF - Serenity Pro) is a new technology that generates a vacuum over the skin and reduces pain in laser-based treatments of the skin, while creating contact between the skin and an upper window. The same technology can be utilized to increase skin blood fraction while operated in a non-contact mode. The objective of this study was to test the enhancement in the efficacy of PWS treatment with PDL and Serenity Pro while vacuum is being utilized in the non-contact, blood-enrichment mode. Fifteen patients with resistant PWS underwent 1-4 treatments (interval of 5-20 weeks) under general anesthesia with a 595-nm PDL at 10-14 J/cm(2), 1.5-3 ms pulse duration, and 7-mm spot size. Lesion blanching with DCD chilling and with vacuum were photographed and compared. Better blanching of various degrees was observed on resistant PWS with the blood-enrichment technique in seven out of 11 patients who returned for follow-up. There were no cases of decrease in efficacy. Blood enrichment with the Serenity Pro non-contact vacuum technology has the potential of enhancing the capability of treating resistant port wine stains in over 50% of cases. Further studies will better quantify the number of treatments necessary for better lesion clearance. The vacuum-assisted technique may be of particular importance in view of the fact that achieving complete lesion clearance remains a challenge in PWS treatments.