Due to its thermodynamic properties, water as a refrigerant (R718) may be applied very efficiently for chiller and heat pump applications with temperature lifts ΔT > 40 K. However, R718 also requires compressors with high flow rates and high pressure ratios. Previous studies indicate that screw spindle compressors, currently used in vacuum pumps, are a promising compressor technology for R718. The authors previously presented a first optimization of a conical screw spindle compressor geometry for a chiller application. The optimized rotor design theoretically allows high volume flows (up to 10,400 m3/h) and high temperature lifts (up to ΔT = 60 K) for chiller applications with evaporating temperatures of 5 °C. This paper focuses on the thermodynamic analysis of the conical screw spindle compressor. The analysis includes the resulting internal leakages and effects of liquid injection. The results indicate a high volumetric and isentropic efficiency for the design operating conditions.