In the present article, two-stage transcritical cycle with expansion valve (TSTCEV) and two-stage transcritical cycle with vortex tube (TSTCVT) are compared mainly on the basis of the second law of thermodynamics. Natural refrigerant nitrous oxide (N2O) is used in both cycles for thermodynamic analysis. The gas cooler and evaporator temperatures are varied from 35°C to 55°C and −55°C to 5°C, respectively. The effects of various operating parameters on the optimum intercooler and gas cooler pressures, the coefficient of performance (COP), exergy destruction and the exergetic efficiency are presented. A component-wise exergy analysis of TSTCEV and TSTCVT shows that the use of the vortex tube instead of the expansion valve reduces the total exergy destruction and increases the exergetic efficiency as well as COP. The exergetic efficiency of TSTCVT is on average 9.17% to 11.68% higher than that of TSTCEV for considered operating conditions. Furthermore, the optimum intercooler and gas cooler pressures in TSTCVT are lower than those of TSTCEV. These results offer significant help for optimum design and the selection of appropriate operating conditions of TSTCVT using refrigerant N2O.