Cogeneration is commonly recognized as one of the most effective solutions to achieve the increasingly stringent requirements in primary energy consumption reduction and greenhouse emissions reduction. The potential of cogeneration led to the adoption of specific directives promoting this technique. In addition, distributed generation plays a strategic role in power reliability. The study and prototyping of cogeneration plants has thus involved many research centers. Similar activities were carried out by DiME (University of Naples). These activities highlighted the need to study the cogeneration system-user interaction to estimate the real energetic and economic benefits. The paper develops a specific methodology that is used to conduct an analysis on the loads of a specific hospital facility. The energetic and economic benefits generated by CHP plants depend on plant and user characteristics, plant layout, management strategies, and economic variables. Therefore, the potential benefits that have attracted the attention of the scientific community are not always granted. For this reason, a predictive analysis is needed to find the optimum configuration of the plant (i.e., engine size, plant configuration, management strategies, absorption chiller size, engine number) that approaches the best energetic solution while ensuring a reasonable profit. Therefore, this study attempts to determine the optimal configuration through a multi-objective approach. (C) 2012 Elsevier Ltd. All rights reserved.