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In order to reduce the energy consumption of HVAC systems in buildings, the use of energy-saving solutions is necessary. One of these solutions is ventilation, which is usually used for maintaining acceptable indoor air quality and thermal comfort. As the change in outdoor environment is unpredictable and the occupant control is spontaneous, it is critical to control the windows and HVAC systems to achieve a maximum use of outdoor air for indoor ventilation. A new rule-based control strategy that could change the opening factor of windows is proposed in this study and its effectiveness was tested in five representative climates, ranging from a subtropical region to a severely cold region. A building model was set up and the indoor air temperature and energy consumption were predicted using EnergyPlus. The results show that the proposed control strategy can utilize ventilation to maintain a comfortable indoor environment with an annual uncomfortable percentage in an occupied period lower than 5%, thus leading to an energy-saving rate of 13.5–55.6%. The simulation results indicate that there are periods of ventilation available during the summer in climate zones with hot summers and warm winters, whereas the control strategy has a better energy-saving performance in temperate areas. This study conducted a preliminary exploration for practical applications of the combined operation of controllable natural ventilation and HVAC systems in buildings. [ABSTRACT FROM AUTHOR]