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Cryogen spray cooling has been applied to protect epidermis from thermal damage in laser dermatology. However, present cryogen R134a shows insufficient cooling capacity on minimizing the laser energy absorption by the melanin in darkly pigmented human skins. With lower boiling point, R404A has potential to improve the cooling capacity. This paper presents an experimental study on the temporal and spatial variation in surface temperature and heat flux during spray cooling using R404A by a straight tube nozzle with expansion chamber, which significantly improves the atomization effect. The experimental results indicate that the temporal and spatial conditions strongly influence the uniformity of surface heat transfer. There exists a sub-region of uniform cooling with radius of 2 mm around spray center with high transient heat flux above 400 kW/m2, which is conducive for physicians to control the therapy area precisely with enhanced laser energy.