We propose computational strategies and algorithms to perform multi-reference Møller–Plesset (MR-MP2) calculations efficiently for large molecules. As zeroth-order reference we employ restricted configuration interaction wave functions expressed in terms of an active space of Hartree–Fock one-particle functions (RAS-CI). To accelerate the convergence of the perturbation expansion and to keep the zeroth-order spaces as small as possible (i.e. Dim<1000) we use improved (average) virtual orbitals. The length of the first-order space (single and double excitations with respect to all reference configurations) is reduced by selecting the most important configurations from the full space based on the magnitude of their H₀ diagonal matrix element. The two-electron integrals in the MO basis are calculated semi-directly with the resolution of the identity (RI) method which avoids computationally demanding 4-index transformations. The errors introduced by the approximations can systematically be reduced and are found to be insignificant in applications to chemical problems. As examples we present MR-MP2 results for excitation and reaction energies of molecules for which single-reference perturbation theory is not adequate. With our approach, investigation of systems as large as porphin or C₆₀ are possible on low-cost personal computers.