The paper gives results of a thermodynamic evaluation of five alternative refrigerants in a vapor-compression refrigeration cycle, utilizing throttling, superheating, and combined throttling and superheating. Five alternative refrigerants (R32, R125, R134a, R143a, and R152a) were considered for refrigerants R12, R22, and R502. Thermodynamically, the best alternative for R12 in a wide range of evaporation and condensing temperatures is R152a, which should be applied in a cycle without internal heat exchange. The second alternative is R134a, which should be applied in a cycle with internal heat exchange. Between R143a and R125, both of which should be applied in a cycle with internal heat exchange, the better replacement thermodynamically for R502 is R143a, particularly at high condensing temperatures. At low condensing temperatures, R125 is to be considered, especially if extended internal heat exchange is applied. As a replacement for R502, R32 has good performance and much higher volumetric capacity. However, excessively high discharge temperatures contraindicate its use, particularly with hermetic and semi-hermetic compressors. No internal heat exchange should be applied with R32, and extreme care should be taken to prevent superheating in suction lines.