The comfort level and well being of building occupants is affected, among other factors, by radiant and air temperature, air quality, air movement, humidity, as well as the degree to which they can control their environment. In the recent years, due to the temperature increase and air quality decrease in urban areas, ventilation systems became more common, in order to meet the requirements to ensure adequate air quality and acceptable indoor temperature. Sustainable methods, such as passive cooling with natural ventilation, have not been yet successful to be used as the only ventilation system, which can fully provide comfortable indoor environment in every building. Moreover, even though the passive systems are efficient, they are dependent to the parameters, such as wind condition, temperature fluctuations, thermal mass of the building elements, etc., which makes them rather difficult to predict and control. Typical conventional climate control systems, operated by fossil fuels, are able to maintain consistent indoor condition against the changing outdoor climate condition. However, these systems are usually not sustainable. For instance, it is estimated that, ventilation systems account for 30% of the energy demand for office buildings. The energy consumption and comfort level provided by a ventilation system depend on the different factors, including the efficiency of the system, air distribution, placement of the air inlets and outlets, air leakage, operation schedule, temperature set points, airflow rate, etc. Conventional ventilation systems usually supply fresh and cool air into the space and replace the entire stale room air. The high energy consumption and required ventilation rates could be reduced by cooling down the actual occupied zones instead of the entire space, for instance using displacement ventilation system. Another example in this regard is "personal ventilation system", which has the advantage to deliver the fresh and cool air directly to the occupied breathing zone. Moreover, personal ventilation system offers the occupants the possibility of individual adjustments and control of their own surrounding environment. This dissertation presents the application of computational and empirical methods to evaluate functionality of ventilation systems in architectural spaces with regard to indoor air quality and thermal comfort. The innovative ventilation systems in office spaces are investigated, including displacement and personal ventilation systems. The research application is aimed at improving the personal comfort and productivity of occupants, taking into account the environmental factors and efficiency of the systems. Performance of the studied systems is investigated via objective evaluations by measurements and subjective evaluations based on feedback from occupants. This study also illustrates the utility of CFD (Computational Fluid Dynamics) simulations for the performance evaluation of ventilation systems and the estimation of airflow pattern in the space. Furthermore, the present contribution investigates whether a relatively comprehensive impact assessment of various design variables and input assumptions (e.g., number and location of diffusers and airflow rates in an architectural space) can be established based on a detailed but small number of numerical simulations. The outcome of such study is remarkably helpful to architects, building engineers, and building scientists, to further improve energy efficiency and occupants comfort in ventilated spaces, and to develop and refine prediction models.