Photocatalytic oxidation (PCO) is a promising technology that has potential to be applied in mechanically ventilated buildings to improve indoor air quality (IAQ). However, the major research studies were done in bench-top scale reactors under ideal reaction conditions. In addition, no study has been carried out on the investigation of the ozonation and photolysis effect using a pilot duct system. The objective of this study is the development of methodologies to evaluate the performance of PCO systems. A systematic parametric evaluation of the effects of various kinetic parameters, such as compound's type, inlet concentration, airflow rate, light intensity, and relative humidity, was conducted, and new interpretations were provided from a fundamental analysis. In addition, the photolysis effect under vacuum ultraviolet (VUV) irradiation for a variety of volatile organic compounds (VOCs) was examined for the first time in a pilot duct system. The performance comparison of ultraviolet C (UVC)-PCO and VUV-PCO was also discussed due to the presence of ozone. Moreover, the formation of by-products generated with or without ozone generation was fully compared to evaluate the PCO technology.