The usual modeling of dispersion interactions in density functional theory (DFT) is often limited by the use of empirically fitted parameters. In this study, the accuracies of the popular empirical dispersion corrections and the first-principles derived effective fragment potential (EFP) dispersion correction are compared by computing the. DFT-D and HF-D equilibria interaction energies and intermolecular distances of the S22 test set dimers. Functionals based on the local density approximation (LDA) and generalized gradient approximation (GGA), as well as hybrid functionals, are compared for the DFT-D calculations using coupled cluster CCSD(T) at the complete basis set (CBS) limit as the reference method. In general, the HF-D(EFP) method provides accurate equilibrium dimerization energies and intermolecular distances for hydrogen-bonded systems compared to the CCSD(T)/CBS reference data without using any empirical parameters. For dispersion-dominant and mixed systems, the structures and interaction energies obtained with the B3LYP-D(EFP) method are similar to or better than those obtained with the other DFT-D methods. Overall, the first-principles derived-D(EFP) correction presents a robust alternative to the empirical-D when used with the B3LYP functional for dispersion-dominant and mixed systems or with Hartree-Fock for hydrogen-bonded systems.