The present disclosure relates to envelope power supply calibration of a multi-mode RF power amplifier (PA) to ensure adequate headroom when operating using one of multiple communications modes. The communications modes may include multiple modulation modes, a half-duplex mode, a full-duplex mode, or any combination thereof. As such, each communications mode may have specific peak-to-average power and linearity requirements for the multi-mode RF PA. As a result, each communications mode may have corresponding envelope power supply headroom requirements. The calibration may include determining a saturation operating constraint based on calibration data obtained during saturated operation of the multi-mode RF PA. During operation of the multi-mode RF PA, the envelope power supply may be restricted to provide a minimum allowable magnitude based on an RF signal level of the multi-mode RF PA, the communications mode, and the saturation operating constraint to provide adequate headroom.