An optimal operation method based on weighted efficiency for a two-stage boost converter is proposed in this study. Detailed loss analysis of the converter is performed to derive the optimal operation method according to the load and input voltage fluctuations, and the optimal DC-bus voltage is derived by applying the weighted efficiency method. The proposed method can satisfy optimal efficiency in the main operation region without a complicated control method. Using 1kW typical two-stage boost converter and is verified three types of weighted efficiency formulas and loss analysis are utilized to derive high-efficiency optimal DC-bus voltage from each load range.