Laser treatment of port-wine stain (PWS) might be improved using a deeply penetrating wavelength. PWSs in 17 patients were treated 3 times with a 595-nm pulsed dye laser (PDL) and a 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Fluences of 1.0, 0.8, and 0.6 times the minimum purpura dose (MPD) were used for Nd:YAG laser. Posttreatment biopsy specimens were taken. Blind assessment and quantitative analysis of PWS clearing were performed from digital photographs. MPD for Nd:YAG laser varied widely, from 40 to 250 J/cm 2 . Purpura lasted longer after PDL. Treatment achieved similar 50% to 75% clearing with both PDL and Nd:YAG laser at 1 MPD. Nd:YAG caused greater perivascular and epidermal injury. Scarring occurred in the only patient treated with a Nd:YAG fluence greater than 1 MPD. Patients preferred Nd:YAG laser because of their faster recovery. Nd:YAG laser used at MPD is as effective as PDL for treating PWS. Nd:YAG laser fluences higher than MPD may cause scarring.