R-410A was invented and patented by Allied Signal (now Honeywell) in 1991. Other producers around the world have been licensed to manufacture and sell R-410A, but Honeywell continues to be the leader in capacity and sales. R-410A was successfully commercialized in the air conditioning segment by a combined effort of Carrier Corporation, Emerson Climate Technologies, Inc., Copeland Scroll Compressors (a division of Emerson Electric Company), and Allied Signal. Carrier Corporation was the first company to introduce an R-410A-based residential air conditioning unit into the market in 1996.

R-410A has replaced R-22 as the preferred refrigerant for use in residential and commercial air conditioners in Japan, Europe, and the United States.

Parts designed specifically for R-410A must be used, as R-410A operates at higher pressures than other refrigerants. R-410A systems thus require service personnel to use different tools, equipment, safety standards, and techniques. Equipment manufacturers are aware of these changes and require the certification of professionals installing R-410A systems. In addition, the AC&R Safety Coalition has been created to help educate professionals about R-410A systems

R-410A cannot be used in R-22 service equipment because of higher operating pressures (approximately 40 to 70% higher).

While R-410A has negligible fractionation potential, it can't be ignored when charging.

To avoid fractionation as the system is charged and for optimum system performance, the correct type of cylinder has to be used for charging - if cylinder with dip-tubes are used, R-410A can be charged while the cylinder is upright. However, if the cylinder doesn't have dip-tubes, it should be kept upside-down to charge with liquid, not vapor, from the cylinder. The procedure, then, is to fill very slowly, the valve restricting output, in order to avoid slugging the compressor with liquid.

Unlike alkyl halide refrigerants that contain bromine or chlorine, R-410A (which contains only fluorine) does not contribute to ozone depletion and is therefore becoming more widely used, as ozone-depleting refrigerants like R-22 are phased out. However, R410A has a high global warming potential of 2088, higher than that of R-22, and an atmospheric lifetime spanning decades.

Since R-410A allows for higher SEER ratings than an R-22 system by reducing power consumption, the overall impact on global warming of R-410A systems can, in some cases, be lower than that of R-22 systems due to reduced greenhouse gas emissions from power plants. This assumes that the atmospheric leakage will be sufficiently managed.

R-410A use is expanding globally and rapidly. While there is some speculation regarding its retirement, there were no generally accepted alternatives for use in commercial air conditioning systems—especially when flammability is considered—though many companies were researching options