This paper discusses the application of exergy analysis to a district heating network (DHN) currently in operation in Brescia (Italy). The purpose is to compare the existing system design with that resulting from an exergonomic analysis. To this aim a general mathematical model is formulated to account for irreversibilities due to the temperature and pressure losses as well as for the assessment of exergy exergy costs for each stream. The objective function is stated as the sum of capital, operational, and maintenance costs of the whole DHN. Such a function is minimized by using two different approaches: an iterative procedure and a genetic algorithm; the latter proves To be particularly suited for this type of problem. Both methods lend to comparable outcomes in terms of minimum cost and plant arrangement. Finally, the optimum configuration is compared with the existing one and shows that the actual network is far from an optimum design both from a thermodynamic and an economic standpoint. Such a procedure could be used profitably in the design of any future DHN.