The refrigerant with the highest global warming potential is R-404A. R-404A is a hydrofluorocarbon (HFC) commonly used in commercial refrigeration systems. It has a global warming potential (GWP) of 3,922, which is significantly higher than other commonly used refrigerants such as R-134a (GWP of 1,430) and R-410A (GWP of 2,088).