BACKGROUND AND OBJECTIVES Improved laser treatment of cutaneous hypervascular lesions is expected by utilizing higher incident dosages, longer pulse durations and longer wavelengths than those currently used in clinical settings. However, simply increasing the incident dosage will also increase the risk of nonspecific thermal injury to the epidermis due to light absorption by melanin. In this study, we investigated the thermal response of human skin epidermis to 595-nm wavelength laser irradiation at high incident dosages (up to 20 J/cm(2)) and long pulse durations (up to 40 milliseconds) in conjunction with cryogen spray cooling (CSC) using ex-vivo human skin samples. STUDY DESIGN/MATERIALS AND METHODS The Candela V-beam trade mark laser (595-nm wavelength) was used in the experiments. Ex-vivo human skin samples (Fitzpatrick types I-VI) were irradiated at the incident dosages D(0) = 4, 6, 10, 15, and 20 J/cm(2), laser pulse durations tau(laser) = 1.5, 10, and 40 milliseconds, without and with CSC (refrigerant-134A, spurt duration tau(CSC) = 100 milliseconds). Thermal injury to the epidermis was evaluated by histological observations. RESULTS Under the same incident dosage, longer pulse durations led to reduced thermal injury to the epidermis. Without CSC, no demonstrable thermal injury to the epidermis was observed in skin types I-II irradiated at the incident dosage as high as 15 J/cm(2), and in skin types III-IV at 10 J/cm(2). When CSC was applied, no evidence of thermal injury to the epidermis was present in skin types I-II even when irradiated at the maximum available incident dosage of the laser system (20 J/cm(2)). In skin types III-IV, no demonstrable thermal injury to the epidermis was observed when using incident dosage as high as 15 J/cm(2) in conjunction with CSC. In skin type VI, thermal injury to the epidermis could not be avoided even at the setting D(0) = 4 J/cm(2), tau(laser) = 40 milliseconds in conjunction with CSC. CONCLUSIONS For a given incident dosage, longer pulse durations help reduce thermal injury to the epidermis. When a 100-millisecond cryogen spurt is applied, thermal injury to the epidermis can be prevented in ex-vivo skin types I-IV when irradiated at higher incident dosages (15-20 J/cm(2)) than those currently used in clinical settings. Further studies on optimizing the CSC parameters in conjunction with the laser irradiation parameters are needed to protect skin types V-VI from thermal injury to the epidermis.