To fully understand the thermodynamic nature of polymer blends and accurately predict their miscibility on a microscopic level, a hybrid model employing both statistical mechanics and molecular dynamics techniques was developed to effectively predict the total free energy of mixing. The statistical mechanics principles were used to derive an expression for the deformational entropy of the chains in the polymeric blends that could be evaluated from molecular dynamics trajectories. Evaluation of the entropy loss due to the deformation of the polymer chains in the case of coiling as a result of the repulsive interactions between the blend components or in the case of swelling due to the attractive interactions between the polymeric segments predicted a negative value for the deformational entropy resulting in a decrease in the overall entropy change upon mixing. Molecular dynamics methods were then used to evaluate the enthalpy of mixing, entropy of mixing, the loss in entropy due to the deformation of the polymeric chains upon mixing and the total free energy change for a series of polar and non-polar, poly(glycolic acid), PGA, polymer blends.