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Heating, Ventilating, and Air-Conditioning systems (HVAC) consume more than 40% of energy in commercial buildings, according to the Commercial Building Energy Consumption Survey in 2012. Therefore, efforts to reduce HVAC energy consumption would be significant in coping with energy-related issues. In that context and in order to enhance the indoor air quality without compromising for energy consumption, the concept of Dedicated Outdoor Air systems (DOAS) emerged. The literature shows that the integration of DOAS with other HVAC systems has been studied widely, yet the impact of integrating DOAS in parallel with multi-zone Variable-Air Volume systems (multi-zone VAV) for an application requiring high ventilation air has not been researched. Therefore, the objective of this study was to assess the impact of the integration from various aspects. For assessing the impact of implementing DOAS in parallel with multi-zone VAV, a primary school model was simulated in 17 climate zones and in 6 HVAC configurations. The simulations were conducted for conditions of 8,760 hours/year, and their results were compared to the results of a baseline model utilizing multi-zone VAV for handling the ventilation load besides handling the thermal local loads. The assessment considered the impact on energy consumption, thermal comfort, and life cycle cost. The results showed a saving in HVAC energy in all considered climate zones when the DOAS supplied ventilation air at 12.8-15.6o C Dry Bulb Temperature (DBT) and 12.8o C Dew Point Temperature (DPT). The saving in energy ranged from 4% to 40%. In addition, the climate zones with low outdoor latent loads experienced high changes in energy consumption compared to the climate zones with high outdoor latent loads. In terms of the change in thermal comfort, the Fanger Comfort Model was utilized to observe the change from the occupant perspectives. The change among the various configurations did not show a significant difference; the maximum percentage of occupants who would have experienced a difference in the thermal comfort was less than 0.5% in all climate zones. Economically, the energy cost would decrease in a configuration supplying ventilation air through DOAS with conditions of 12.8-15.6o C DBT and 12.8o C DPT in all considered climate zones. In this study, the saving in energy cost ranged from $ 500/year to $ 6,000/year. Moreover, multi-zone VAV units could be downsized significantly. However, the saving would not have been encouraging economically when it was considered for overcoming the cost of implementing DOAS; the payback period was 11 years at the best, only for owning DOAS units without other costs associated with the DOAS implementation.