The local pair natural orbital approach, which has been combined with two post-HartreeFock methods, CEPA-1 and pCCSD-1a, recently, is assessed for its applicability to large real-world problems without abundant computing resources. Test cases are selected based on being representative for computational chemistry problems and availability of reliable reference data. Both methods show a good performance and can be applied easily to systems of up to 100 atoms when very accurate energies are sought after. A considerable demand for basis sets of good quality has been identified and practical guidelines to satisfy this are mapped out. (c) 2012 Wiley Periodicals, Inc.