A fundamental approach to separate azeotropic mixtures by tuning the phase behavior using pressurized CO2 as a tunable solvent was studied. Following this new process concept, two process variants were put forward to separate aqueous pressure-insensitive and pressure-sensitive azeotropic mixtures. The two process variants were studied in process simulations, and the potential was evaluated by comparison with a conventional pressure-swing distillation process for the acetonitrile water system. The new process shows significant potential to reduce the separation costs by 30.5% up to 68.9% for a broad variety of mixtures with water fractions in the range of 0.1 <= x(H2O) <= 0.9. Thus, these results clearly indicate that the novel fundamental separation approach is a promising alternative to conventional processes for the separation of azeotropic mixtures.