Heat extraction from medium-deep thermal energy has become an important research direction in the current geothermal development. In this study, a comprehensive performance evaluation model of a coaxial heat exchanger for the development of medium-deep geothermal resources was established, which combined the formation, wellbore, and heat-carrier fluid flows, as well as the heat transfer and physical property changes. This model was then used to compare and analyze the performances of different heat-carrier fluids and the effects of different well depths and geothermal gradients. Different heat-carrier fluids had significant effects on the performance of the coaxial heat exchanger. Among these, carbon dioxide was the best heat-carrier fluid, with the largest heat output and coefficient of performance. When carbon dioxide was used as the heat-carrier fluid and the well depth structure was determined, there was an injection parameter that produced the optimal performance in the heat exchanger. When coaxial heat exchangers are used to develop medium-deep geothermal energy, the influences of friction and the Joule-Thomson effect cannot be ignored. In formations with large geothermal gradients or wells with large depths, larger tubing and casings should be selected to reduce the negative effects of friction and the Joule-Thomson effect. (c) 2020 Elsevier Ltd. All rights reserved.