This paper investigates the use of several zero-ozone depleting potential (zero-ODP) HFC refrigerants, including HFC-134a, HFC-227ca, HFC-227ea, HFC-236ea, HFC-236cb, HFC-236fa, HFC-245cb, and HFC-254cb, for centrifugal chiller applications. We took into account the thermodynamic properties of the refrigerant and aerodynamic characteristics of the impeller compression process in this evaluation.. For a given operating temperature lift, there are significant differences in the pressure ratio required by each refrigerant and this variation in pressure ratio directly affects compressor size, efficiency, and performance. A comparison of the HFC refrigerant candidates with CFC-114 shows that HFC-236ea, HFC-227ca and HFC-227ea are viable alternatives for centrifugal water chillers. HFC-236ea has properties closest to CFC-114, and will result in comparible performance, but will require a slightly larger impeller and a purge system. Using HFC-227ca or HFC-227ea results in a significantly lower enthalpy rise requirement, potentially allowing single-stage compression, however, wet compression could be a problem. Single-stage compression gives an overall performance advantage over CFC-114 (operating with 3-5 °C of liquid subcooling), and when considering thermodynamics and aerodynamics, as is necessary in centrifugal applications, we find that HFC-227ca and HFC-227ea have additional advantages over HFC-236ea and CFC-114.