Optimization and a cost-oriented analysis, including the capital and energy-of-compression costs, were performed to compare propane- and ammonia-refrigeration economizer cycles with and without presaturators. The simulation and optimization to minimize the cost were performed by using the HYSYS simulator and the Peng–Robinson equation of state was used for the thermodynamic model. Different chiller temperatures and duties were considered. The simulation and optimization results show the limitations of simplified formulas in determining properly the optimum intermediate compression pressure in refrigeration economizer cycles. The results also show that having a presaturator lowers the cost of ammonia refrigeration cycles and enhances costs in propane loops. Among all, ammonia cycles with presaturators were found to offer the lowest cost. The exergy and economic analyses show quite similar distributions of the lost work and cost in the different components of the refrigeration loops. Ammonia refrigeration cycles with presaturators offer the lowest lost work and the highest coefficient of performance. However, the chiller temperatures are limited to approximately −33.3 °C (−28 °F) in the case of ammonia cycles whereas they can be as low as −41.7 °C (−43 °F) in propane loops.