The object of research is the effect of thermohydraulic irreversibility of energy processes in the cycle of a refrigeration machine using an ozone-safe non-azeotropic mixture as a refrigerant on its energy efficiency. One of the most problematic places during the development and design of such refrigeration machines is that, due to the peculiarities of the thermodynamic properties associated with the different chemical composition of the components, non-azeotropic mixtures are characterized by differences in the equilibrium concentrations of the components in the liquid and vapor phases. This property of non-azeotropic mixtures presents a certain difficulty for their effective application in refrigeration machines and heat pumps. During the study, modern methods of analysis and synthesis of thermodynamic systems are used, based on the application of the theoretical apparatus of technical thermodynamics, thermoeconomics, the theory of heat and mass transfer, as well as elements of the theory of systems engineering. The issue of assessing the energy efficiency of the cycles of refrigeration units operating on a non-azeotropic mixture of refrigerants is considered, taking into account the variability of the composition of the components of the mixture. A method has been developed for the formation of the composition of a multicomponent mixture, taking into account the influence of the non-isobarity of processes in the hydraulic circuit of the refrigerant circulation on the energy efficiency of the refrigeration machine. Based on a numerical experiment, the influence of changes in the concentrations of the components of the mixture R32, R125, R134a on the non-isothermal phase transition in the evaporator and condenser, as well as on pressure losses in the hydraulic circuit elements of an autonomous air conditioner, is established. The effect of friction at a temperature level below ambient temperature on the exergy efficiency of the refrigeration machine is analyzed. An advanced exergy analysis of the refrigeration cycle with a non-azeotropic mixture is carried out, as a result of which the avoidable and unavoidable, as well as the endogenous and exogenous components of the destruction of exergy in the elements are determined. The proposed method, due to its visibility, can significantly simplify the finding of the thermodynamic parameters of the refrigerant at the nodal points of the refrigeration machine cycle during numerical simulation.