Three-phase, four-wire, split-capacitor inverters, thanks to their capability to deal with unbalanced systems, are currently employed in photovoltaic installations, electric vehicles battery chargers, active power filters, and many other grid-tied applications. The minimization of ac output current ripple and switching losses positively impacts the inverter's efficiency, volume, weight, and cost optimization. For this reason, a novel variable switching frequency driving strategy independently tunable on each phase is proposed in this article. Taking advantage of phase current ripple prediction, a proper variable switching frequency strategy is applied for obtaining a flat current ripple profile. Having tuned the driving strategy parameters, it is possible to optimize and compare individual metrics such as the maximum peak-to-peak value of the current ripple, current ripple rms, average switching frequency, and switching losses. By applying the proposed modulation method, a significant inverter performance enhancement has been obtained. Converter efficiency is improved without introducing detrimental effects on the current harmonic quality. Analytical derivations are expressed as a modulating index function and the power factor for balanced and unbalanced systems. All the theoretical developments are verified throughout numerical simulations and experimental tests.