This work deals with the risk related to the flammability and toxicity of low Global Warming Potential (GWP) refrigerants used in heat pumps for residential applications. Some new generation refrigerants were analyzed assuming to make a drop-in for a typical 50 kW heat pump, suited for small multi-family buildings (4 ÷ 6 dwellings). The theoretical maximum Coefficient of Performance (COP) was calculated for the selected fluids, identifying the best performing one from an energy point of view. Subsequently, an analysis of some of the potentially more dangerous accident scenarios was performed, considering the outdoor/indoor release of gases. More in detail, two accident scenarios were analyzed, assuming a refrigerant leak from a hole in the pipeline downstream of the heat pump compressor: in one case the gas is released in an open environment with an ignition near the release point (jet fire), in the other case the release happens within a confined environment. In both cases, the conditions in which it is possible to operate safely were determined.