While forced-air convective systems remain the predominant method for heating and cooling worldwide, radiant cooling and heating systems are emerging as a more efficient alternative. Current radiant cooling systems primarily rely on hydronic chilled water systems. This study introduces direct-expansion radiant cooling as a novel technique that could enhance the efficiency of radiant cooling and reduce its environmental impact. Water (R-718) has been tested as a refrigerant due to its favorable thermodynamic properties and environmental advantages; however, to the author’s knowledge, it has yet to be tested in direct-expansion radiant cooling. This research investigated several refrigerants, including water (R-718), ammonia (R-717), R-410a, R-32, R-134a, and R-1234yf, for this application. The findings indicate that water demonstrates efficiency comparable to other non-natural refrigerants, making it a promising candidate, given its favorable thermodynamic properties and substantial environmental benefits. Despite challenges such as a high compression ratio necessitating multi-stage compression, a high compressor discharge temperature exceeding 300 °C and requiring specialized blade materials, and a high suction volume flow rate, direct-expansion radiant cooling operates within a different temperature range. Consequently, the compressor discharge temperature can be reduced to 176 °C, and the compression ratio can be lowered to approximately 3.5, making water a more viable refrigerant option for this application.