A refrigeration system having a main circuit including a main compressor thermally coupled with a secondary or subcooling circuit. The main circuit uses a HFC blend, such as but not limited to, R125/R143A blend or R32/R125/R134A blend as a refrigerant and the subcooling circuit uses an R32 blend. Some embodiments may include more than one main compressor. Some embodiments of the secondary circuit may include more than one secondary compressor. The combined system of differing refrigerants provides increased efficiencies and reduced Global Warming Potential (GWP) over single refrigerant systems for low and medium temperature refrigeration applications.