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This paper presents a novel switching sequence design for the space-vector modulation of high-power multilevel converters. The switching sequences are optimized for the improvement of harmonic spectrum and the minimization of device switching frequency. Compared to other commonly used switching sequences, the output spectrum of the proposed design shows higher inverter equivalent switching frequency. Meanwhile, the device switching frequency is reduced by using a flexible switching pattern. The proposed switching sequence has been simulated and experimentally tested on a 5-level neutral point clamped H-bridge based inverter. The results from both simulations and experiments consistently verify the above-mentioned features.