This paper presents a building automation strategy for natural ventilation control and reducing building energy consumption. An on-off control is proposed in order to manage the windows opening and realize a natural ventilation flow guaranteeing indoor thermal comfort. The control logic is based on activation thresholds that are optimized to reduce the discomfort for overheating and undercooling. In particular, the temperature comfort range dynamically varies according to the adaptive thermal comfort theory. To this aim, a co-simulation architecture is proposed: the thermal building behavior and ventilation dynamics are simulated by TRNFLOW within the TRNSYS software and a Particle Swarm Optimization algorithm is employed to optimize the thresholds of windows opening. A case study focusing on a residential building situated in the Mediterranean climatic context is presented: the thermal comfort analysis shows that the optimized control logic significantly reduces the overheating discomfort.