Abstract In this paper, the mixture of HFC-161/HFC-134a (0.6/0.4 in mass fraction), named ‘M5’, is proposed as a substitution of HFC-134a used in automotive air conditioning systems. The theoretical and experimental cycle performances for M5 and HFC-134a were conducted at the condensation temperature from 50 °C–65 °C, evaporation temperature from −5 °C–10 °C. Theoretical results show that COP of M5 is very close to that of HFC-134a, the specific refrigeration capacity and volumetric refrigeration capacity of M5 are much higher than those of HFC-134a. Experimental results show that COP of M5 is a bit higher than that of HFC-134a, the refrigeration capacity and compressor power of M5 are about 32% and 30% higher than those of HFC-134a, respectively, the compressor discharge temperature and pressure ratio of M5 are about 15% higher and 10.9% lower than those of HFC-134a, respectively. Considering the good performance and compatibility with the existing system, M5 is a potential alternative refrigerant for HFC-134a.