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The utilization of a burst-mode power amplifier (PA) together with pulse-width modulation (PWM) is a promising concept for achieving high efficiency in radio frequency (RF) transmitters. Nevertheless, such a transmitter architecture requires bandpass filtering to suppress side-band spectral components to retrieve the wanted signal, which reduces the transmit power and the transmitter efficiency. High efficiency can only be expected with the maximum transmit power and signals with low peak-to-average-power ratios (PAPRs). To boost efficiency for signals with high PAPRs and signals at variable transmit power levels, the burst-mode multilevel transmitter architecture has been widely discussed as a potential solution. This paper presents an efficiency optimization procedure of burst-mode multilevel transmitters for signals with high PAPRs and signals at variable transmit power levels. The impact of the threshold value on the transmitter efficiency is studied, where the optimum threshold value and the maximum transmitter efficiency can be obtained according to input magnitude statistics. In addition, the relation between the threshold value and the efficiency expression of burst-mode multilevel transmitters and those of Doherty PAs is investigated. It is shown that the obtained optimum threshold value, although originally designed for burst-mode transmitters, can also be applied to Doherty and multistage Doherty PAs to achieve maximum transmitter efficiency. Simulations are used to validate the efficiency improvement of the optimized burst-mode multilevel transmitters compared to two-level and non-optimized multilevel transmitters.