CO2 has been proposed as a working fluid for geothermal energy production because of its ability to establish a self-sustaining CO2 thermosiphon, taking advantage of the strong temperature dependence of CO2 density. To test the concept of CO2 heat extraction, in January 2015 a CO2 thermosiphon was operated at the SECARB Cranfield Site, Cranfield, Mississippi, where a brine-saturated sand at a depth of 3.2 km has been under near continuous CO2 flood since December 2009 as part of a U.S. Department of Energy demonstration of CO2 sequestration, resulting in a partially saturated reservoir surrounding a well pair. The lateral distance between the producer and injector was 112 m at reservoir depth, a distance considered pre-commercial in scale, but great enough that thermal breakthrough was still not significant after several years of injection. Instead of producing power with a turbine, heat was extracted heat from recirculated fluid using a heat exchanger and portable chiller. The well field and surface equipment were instrumented to compare field observations with predicted responses from numerical models. Thermosiphon flow could be initiated by venting, but thereafter flow rate steadily declined, indicating that the thermosiphon was not sustainable. To model the system, the capability of T2Well, a fully coupled wellbore/reservoir numerical simulator, was expanded to enable simulation of the entire loop of fluid circulation in the fully-coupled system consisting of the injection/production wells, the reservoir, and the surface devices (heat exchanger, flow-rate regulator etc.). Combined with the newly developed TOUGH2 equation of state module called EOS7CMA, the enhanced T2Well was used prior to the field experiment to simulate the circulation of a CO2-H2O-CH4 mixture in a model geothermal system patterned after the Cranfield demonstration test. The model predicted that a sustainable thermosiphon could be achieved. After the field thermosiphon did not achieve the pre-test prediction of flow rates and thermosiphon sustainability, the numerical model was modified to improve realism and calibrate certain processes; it was then able to reproduce the major phenomena observed in the field. In a series of sensitivity studies, many factors were found that could potentially contribute to the failing of a sustainable thermosiphon. These factors could be categorized as two types: factors that increase the resistance to flow and factors that increase heat loss of the working fluid. The lessons learned can be applied to both future modeling and to achieving CO2-based geothermal reservoir exploitation.