The applicability of the quantum-chemistry-based model COSMO-RS is investigated concerning the prediction of vapor-liquid equilibria, i.e., prediction of the activity coefficient of a component in a mixture. A broad range of systems was chosen to cover different and significant types of interactions in mixtures of alkanes, alkenes, cycloalkanes, alcohols, ethers, ketones, aldehydes, and alkyl benzenes. Predictions of activity coefficients and phase behavior are presented and compared with experimental data.