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A newly developed, non-ozone-depleting refrigerant blend containing a fluoroiodocarbon compound was compared with R-22 in a laboratory-scale, water-to-water refrigeration cycle test loop. The loop is equipped with a coaxial tube-in-tube condenser, a baffled shell-in-tube evaporator, and a variable-speed compressor. The blend and R-22 were tested at saturated evaporator temperature conditions of about −10 °F to −20 °F and saturated condenser temperature conditions from about 80 °F to 100 °F. The compressor speed was varied such that evaporator (cooling) capacity was held constant at approximately the same value for both refrigerants for each test condition. To maintain equal capacity, results showed the compressor speed for the blend to be at least 53% greater than that for R-22. Measured system efficiency with the blend was at least 25% better than for R-22 for near equal operating temperature and capacity conditions. When allowing for maximum impact of the experimental uncertainties, the minimum COP improvement observed for the blend was about 10%. Ideal cycle calculations using the best available property estimates for the blend and the compressor efficiencies observed during the tests also suggested a 10% improvement for the blend over R-22 (almost all due to better isentropic efficiency of the compressor with the blend). Better thermodynamic property data are needed for the blend and further investigations are needed to fully assess its potential for refrigeration equipment applications.