A study was made to determine the solubility behavior of 17 ionic liquids (ILs) with asphaltenes and a quantum-chemical density functional theory approximation using a def-TVZP basis set and the PerdewBurkeErnzerhof functional. The conductor-like model from COSMO-RS was used within the real solvent approximation to determine the density, molar volume, viscosity, and heat capacity with a statistical thermodynamic treatment of the interacting surface charges of the individual molecules. The solubility parameter of ILs and asphaltenes was determined using the relationship of the density and solubility parameters proposed by Panuganti et al. (Ind. Eng. Chem. Res. 2013, 52, 80098020). The results of the thermodynamic and solubility parameters were compared with the experimental data, and a close agreement was verified. The relative solubility of the asphaltenes with respect to ILs was determined using the d values and Hansens method, i.e., spheres approximation. The structure and size of the cation (including the cationic ring head and the alkyl chain length) of ILs have an influence on their ability for dispersing asphaltenes according to the molecular interactions that govern the miscibility behavior of ILs and asphaltenes, i.e., van der Waals, pi pi, cation-pi, and hydrophobic interactions.