Operable windows provide occupants with the ability to control local environments and satisfy human expectation to access outdoor environments. Operation behaviors or strategies for operable windows have substantial impacts on the indoor environment and building energy consumption. Facility managers complain about operable windows left open in buildings with conventional HVAC systems. However, optimum control strategies of window operation reduce energy consumption for buildings via natural ventilation or mixed-mode ventilation. This study focuses on the investigation of the impacts of window operation on building performance for different types of ventilation systems including natural ventilation, mixed-mode ventilation, and conventional VAV systems in a medium-size reference office building. A building performance simulation tool-EnergyPlus-is used to simulate window operation for each system type. Various control strategies of window operation, simulated using the energy management system feature (EMS) in EnergyPlus, are evaluated based on the criteria of thermal comfort and energy consumption. The investigation included the interaction between conventional VAV systems and window operation as well as control strategies for natural ventilation and mixed-mode ventilation. The results highlighted the impacts of window operation on energy use and comfort and identified HVAC energy savings of 17-47% with mixed-mode ventilation during summer for various climates. (C) 2015 Elsevier B.V. All rights reserved.