The comprehensive understanding of phase behaviors of mixtures containing acetic acid have been a focus of much research. Both experiments and simulations have indicated the formation of various local fluid structures of acetic acid, including the cyclic dimer, the chain network, and solventacid hydrogen-bonded dimers. Conventional modeling approaches either fit the model parameters to experimental data, or introduce new parameters to account for the change of properties due to molecular association. Here, we propose a new approach for modeling such systems without readjustment of the parameters in the predictive thermodynamic model. In this approach, the significant local fluid structures are considered explicitly as new species, and the transition of acetic acid in different forms (monomer and various dimers) are considered via chemical reactions. Using the PR+COSMOSAC equation of state, we show that accurate vaporliquid equilibrium can be described only when all the significant local fluid structures are included. For example, the prediction accuracy from this approach for 9 binary mixture (502 data points, temperature range from 293.15 K to 502.9 K) of acetic acid with alcohols or water reduces from 35.28% and 11.68% (for pressure and vapor composition, respectively) to 5.23% in pressure and 2.26% in vapor composition when the cross-associated dimers are included in the calculations. This is also slightly more accurate compared to those (7.29% and 2.71%) from the modified UNIFAC model combined with the HaydenOConnell model for vapor-phase nonideality. This new approach provides not only quantitative predictions of phase behaviors involving acetic acid, but also insights to the transition of local fluid structures with mixture composition.