To identify low GWP refrigerants to replace R-22 and R-410A, extensive experimental evaluations were conducted for multiple candidates at standard test conditions and at high-ambient conditions. R-22 was compared to R-290, DR-3, ARM-20B, N-20B and R-444B in a mini-split air conditioning unit originally designed for R-22; R-410A was compared to R-32, DR-55, ARM-71A, and R-447A in a mini-split unit designed for R-410A. In addition, the experimental data was used to calibrate a physics-based equipment model, i.e. ORNL Heat Pump Design Model (HPDM).