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The special using condition of high-power three-level explosion-proof inverter limits its cooling system within heat pipe and water-cooled cooling systems. How to calculate these two systems quantitatively to provide references for engineering application becomes one of the critical problems. In this paper, the principle of three-level explosion-proof was introduced first, and the power-loss generation theory was described and deduced into equations. Secondly, the heat pipe cooling system theory calculation was conducted based on the power losses of power devices, and the whole cooling system model was built by using finite element analysis. Finally, the temperature rise experiment was carried out on a 1 MW high-power three-level explosion-proof inverter, and the results proved the feasibility of this theory and its accuracy of analysis.