Improved laser treatment of port wine stains is expected by utilizing higher incident dosages, longer pulse durations, and longer wavelengths than those currently used in clinical settings. However, higher incident dosages also increase the risk of nonspecific thermal injury to the epidermis. Using ex-vivo human skin samples, we investigated the thermal respone of human skin epidermis in different skin types ot 595-nm wavelength laser irradiation at high incident dosages (up to 20 J/cm2) and long pulse durations (1.5 to 40 milliseconds) in conjunction with cryogen spray cooling (CSC). Human skin samples (Fitzpatrick types I-VI) from consenting adult females undergoing trans-rectus abdominis myocutaneoues flap procedures were irradiated at the incident dosages D0=4, 6, 10, 15, and 20 J/cm2, pulse durations τlaser=1.5, 10, and 40 milliseconds without and with CSC (Refrigerant-134A, spurt duration τCSC=100 milliseconds). Thermal injury to the epidermis was evaluated by histological observations. Experimental results showed that thermal injury to the epidermis could not be avoided in skin type VI even at D0 = 4 J/cm2 in conjunction with CSC. However, CSC allowed utilization of high incident dosages (15 - 20 J/cm2) in skin types I-IV. Under the same incident dosage, longer pulse durations led to decreased degree of thermal injury to the epidermis. Threshold values for irradiation parameters that resulted in thermal injury to the epidermis for each skin type were obtained.