Auto refrigerant cascade (ARC) refrigerators are used extensively in the semiconductor manufacturing industry to provide refrigeration in the temperature range of 80–150 K. The performance of the ARC refrigerator depends on the mixture composition, operating pressures, etc. ARC refrigerators employ one or more liquid–vapor phase separators to separate the compressor lubricating oil and the condensed high boiling components and return to the compressor at an intermediate temperature to prevent freezing of the compressor lubricating oil and high boilers at low temperatures. However, dry-out of the phase separator can occur at some conditions. The phase separator dry-out phenomenon in ARC refrigerators has been studied experimentally with different mixtures and operating temperatures, the results of which are reported in this paper. The results of the studies show that the temperature difference between the streams at the cold end of the first heat exchanger can be used to reliably predict the dry-out of the phase separator.