Electronic devices with wireless communications capabilities are provided. The electronic device may include storage and processing circuitry, power amplifier circuitry, power supply circuitry, etc. The storage and processing circuitry may direct the power amplifier circuitry to operate using a desired gain mode, in a particular radio channel, and at a given output power level. The power supply circuitry may bias the power amplifier circuitry with a power supply voltage. The performance of the power amplifier circuitry may be characterized by an adjacent channel leakage ratio (ACLR) margin. The power consumption of the power amplifier circuitry may be characterized by a current savings ratio. A cost function may be calculated by taking the product of the ACLR margin and current savings ratio. A minimum point for each cost function curve may be determined. It is desirable to bias the power amplifier circuitry with a supply voltage corresponding to the minimum point.