This paper proposes a new efficient model for the prediction of low-amplitude ground-borne vibrations in buildings. The model takes into account the three-dimensional nature of the building structure by analytical and semianalytical means, making it ideal for performing parametric studies or large-scale vibrations predictions. Its formulation assumes that the principal component in floor vibrations is the vertical one and assumes that the vibrations are transmitted to the various floors through the building columns. The correctness of the model is tested by comparing, in two 3-story building examples, its results with those obtained using a numerical model. Results regarding the isolation efficiency of implementing a thicker lower floor or columns with a larger cross section are also presented. The building-soil coupling is formulated considering piled foundations in a stratified soil. To ensure the computational efficiency of the calculations, the piles’ response to an incident wavefield is modeled considering the Novak pile model for a layered half-space. Finally, a study of the importance of the soil mechanical parameters in the considered problem is conducted using the building-soil coupled model.