© 2021 Elsevier LtdIn contrary to current studies in the literature, mostly concerning continuously operation system, this paper explores the effect of heating/cooling operation schedule on the determination of optimum insulation thickness (OIT) and location by studying different intermittent heating and cooling strategies. With this aim, two different cases, corresponding to house and office, were investigated for the climatic conditions of Ankara, Turkey, and compared with the continuous case. Performed analyses show that the optimum insulation thickness is highly dependent on the operation mode of buildings. When an intermittent heating and cooling strategy is applied, the OIT values remarkably differ from the continuous case (reducing by up to 2 folds), showing potential savings resulting from the energy management system. Locating the insulation material at the external wall surface was found to be more effective irrespective of the operation mode of the building. Furthermore, effects of applying OIT under the intermittent operation on the indoor air temperature fluctuations, energy consumption and level of greenhouse gas emissions are investigated. Most profound energy savings are observed for heating mode. For all the studied cases, the reduction in the total energy and global warming potential is between 52–74%, and 37–62%, respectively.