A new Monte Carlo computer simulation method is presented for performing property predictions for fluid systems at fixed entropy using a molecular-level system model. The method is applicable to both non-reacting and reacting systems, and can be applied to the design of isentropic processes important in refrigeration and heat pump cycles, and for fluid compression and expansion processes. The details of the method are presented, and we illustrate its application for isentropic calculations involving compression of the alternative refrigerant HFC–32 (CH2F2). Calculations are also presented using the approach to predict fluid state properties and the coefficient of performance for a vapor-compression refrigeration cycle.