The present paper describes an Energy Management System developed to operate a polygeneration microgrid where demand response strategies are applied. The proposed tool is characterized by a detailed representation of generation units and flexible loads, as well as electric/thermal networks and storage systems. Furthermore, the interaction between the microgrid and a smart building is modeled, taking into account the inner comfort level in the objective function of the optimization problem. The tool is applied to a real case study represented by the Savona Campus of the University of Genoa in Italy, where a polygeneration microgrid and a smart building are present.