A comparison of energy, exergy rate and economic analyses for an air conditioning ON/OFF cycle and variable frequency drive (VFD) HVAC systems with heat-mass exchange calculations were performed. The study considered several key performance parameters including; energy consumption, energy saving, exergy destruction rate, exergy efficiency, CO2 emission, the coefficient of performance (COP), and cost analysis for both HVAC systems. The total energy consumption, exergy destruction, and CO2 emission are lower when a VFD HVAC is used, as compared with an ON/OFF cycle HVAC system. The total exergy destruction decreases by more than 20%, on average, when a VFD is used when compared with the case of the ON/OFF cycle. Thus, this study reveals that, when a VFD is used, the energy efficiency and exergy efficiency increase by more than 37% and 10%, respectively.