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Libraries and archives house a majority of cultural heritage objects. The main purpose of libraries and archives is to provide suitable indoor climate conditions for preservation of their collection. In general, a large bulk of hygroscopic material is present which aids stable indoor climate conditions. Limited disturbances due to visitor presence occur in repositories and excludes to a large extent thermal comfort requirements. Library archives show potential of more tolerant setpoint control with permissible fluctuations. Little research is present into dynamic setpoint control and intermittent conditioning in libraries and archives. The aim of this study is to explore the possibility for intermittent conditioning and dynamic setpoint control on the energy impact and microclimate behavior in a library case study in The Netherlands. By means of a hygrothermal monitoring campaign from August 2016 to August 2017 the current indoor climate has been assessed under regular conditions and intervention periods (summer and winter) where the air handling unit was turned off. Both temporal and spatial measurements provided important information on microclimate behavior of the investigated repositories. A validated multi-zone model was used to investigate multiple setpoint strategies. Results show the potential of intermittent conditioning depending on whether dynamic setpoint conditions are used during operational hours (e.g. ASHRAE climate classes). If static conditions are applied, energy demand increases significantly, however, under dynamic setpoint control significant energy savings are possible. The lifetime multiplier is used to assess the chemical risks. The majority of investigated setpoint strategies show increased chemical risk.