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Hydrofluorocarbons (HFCs) are the fastest growing type of greenhouse gases (GHG) emissions, increasing at an annual rate of 10-15% . HFCs are primarily used as refrigerants in air conditioning and refrigeration equipment and have a global warming potential (GWP) many thousands of times greater than CO2. Their rapid growth has led to a global agreement to aggressively phase down their production by amending the Montreal Protocol on Substances that Deplete the Ozone Layer . We quantify the GHG benefits implementing aggressive but economic energy efficiency measures (about 30% more efficient than current technology) in air-conditioning (AC) and large commercial refrigeration equipment (CRE) together with low-GWP refrigerants. Shifting the 2030 world stock of room ACs and CRE from current levels of energy-efficiency and high-GWP refrigerants to “economic” energy efficiency levels and low-GWP refrigerants would avoid up to 240.1 GT CO2e by 2050 and shifting to “best-available technology” energy efficiency levels and low GWP refrigerants would avoid up to 373 GT CO2e by 2050 with existing electricity grid emission factors. About two-thirds of this cumulative savings are from reduced electricity sector emissions from improved energy efficiency. Thus, it is highly beneficial to pursue high energy efficiency in concert with the transition to lower GWP refrigerants to achieve maximal GHG reductions with the least amount of equipment re-design and replacement.