In this study, the performance characteristics of an R404A indirect refrigeration system (IRS) applied to an internal heat exchanger (IHX) is evaluated for supermarkets and hypermarkets. In a direct expansion system, R404A is the primary refrigerant and R744, a brine, is the secondary fluid. While there are abundant studies analyzing the theoretical performance of IRS, experimental research on IRS is lacking, and there are no papers that address the results of changes in the IHX in detail. In this study, the results achieved by modifying various parameters are experimentally evaluated to provide fundamental data for designing the optimal IRS. In the main results, looking at the trend of the increase in IHX efficiency, the change is very minimal when the efficiency is above 50%, so it is ideal to apply an IHX efficiency of about 50% considering economics and COP, etc. Applying the results in this study enables the operation and maintenance of IRSs as an eco-friendly system by achieving energy efficiency through optimizing the system coefficient of performance and securing economic feasibility by minimizing the R404A charging amount of the refrigeration cycle. To serve supermarkets and hypermarkets, R744 as a secondary fluid may help to realize an ecologically friendly, compact IRS system with a high heat transfer coefficient that can operate at low temperatures (−35 to 5 °C).