An interface between ab initio quantum mechanics (QM) methods and the general effective fragment potential (EFP2) method, QM-EFP2, is implemented in which the intermolecular interactions between a QM molecule and EFP fragments consist of Coulomb, polarization, exchange repulsion (exrep), and dispersion components. In order to ensure accuracy in the QM-EFP2 exrep interaction energy, the EFP2-EFP2 spherical Gaussian overlap (SGO) approximation is abandoned and replaced with the exact electron repulsion integrals (ERI) that are evaluated with a direct method to reduce disk usage. A Gaussian damping function for the QM-EFP2 Coulomb component damps both the EFP nuclear and electronic charges. A new overlap damping function has been implemented for the QM-EFP2 dispersion component. The current QM-EFP2 implementation has been benchmarked with the S22 and S66 data sets and demonstrates excellent agreement with symmetry-adapted perturbation theory (SAPT) for component energies and with coupled cluster theory [CCSD(T)] for the total interaction energies. Water clusters of various sizes (up to 256 water molecules) have been tested; it is shown that the QM-EFP2 method has an accuracy that is comparable to that of EFP2-EFP2. It has been shown previously that the accuracy of EFP2-EFP2 intermolecular interactions is comparable to that of second-order perturbation theory (MP2) or better. The implementation of the distributed data interface (DDI) parallelization scheme significantly improves the efficiency of QM-EFP2 calculations. The time to form the QM-EFP2 Fock operator per SCF iteration for water clusters scales linearly with the number EFP basis functions.