Quantitative Structure-Property Relationship (QSPR) models for prediction of various thermodynamic properties of simple organic compounds have been developed. A number of new descriptors are proposed and used alongside with descriptors available within the Codessa program. An important feature in this work has been to include the most probable molecular conformers in the model development and thus account for the conformational flexibility of the molecules. The models cover the properties boiling points, melting points, enthalpies of vaporization, enthalpies of fusion, and liquid densities for alkanes, alcohols, diols, ethers, and oxyalcohols, including cyclic alkanes and alcohols. Several good models, having good predictability, have been developed. To enhance the applicability of the QSPR models, simpler expressions for each descriptor have also been developed. This allows for the prediction of the physical properties by knowledge of the molecular constitution only.