Ejector cooling cycle has considerable potential for sub-ambient refrigeration cooling. The mechanical compressors in traditional cooling cycles can be replaced by ejectors, so-called thermal compressors. Instead of using electricity, an ejector utilizes abundant low-grade heat, such as waste heat or solar energy, to provide refrigeration cooling. Moreover, the mechanism of an ejector makes the choice of refrigerants very flexible. Although an ejector has the attributes of simplicity, reliability and low maintenance, its performance is limited by inappropriate design. Therefore, designing high-performance refrigerant ejector becomes essential to achieve their wide deployment in sub-ambient cooling applications. In this work, systematic computational Fluid Dynamics (CFD) studies were performed to model a 2-D axisymmetric ejector, which was further validated with available experimental data. In addition to the performance prediction, the CFD ejector model provides the local flow field and shock waves for further physical understanding of ejector cooling. Moreover, an improved ejector design is proposed to enhance the refrigeration cooling performance. A design study of ejector with environment-friendly refrigerant (HFO) is presented to demonstrate its capability in sub-ambient refrigeration cooling applications.