The use of organic Rankine cycles (ORCs) is a viable solution for the recovery of waste heat. For an air separation unit (ASU) with a production of V˙O2=58300mN3/h operating in Romania, the value of utilization of the heat transferred to the cooling system of the compression area represents 21% of the global system electrical energy input. To recover this thermal energy and transform it into mechanical energy, an ORC system was proposed. To maximize the production of mechanical power, an exergy analysis was performed. Exergy analysis was used to choose the most suitable organic fluid and find the optimum constructive structure of the Rankine cycle. The calculation of the exergy destruction in the key apparatuses of the system allowed investigation into the optimization search procedure. The large exergy destruction in the liquid preheater suggested the decrease in the temperature difference in this part of the evaporator by increasing the inlet temperature of the liquid; and an internal recuperative heat exchanger was used for this purpose. When permitted, the overheating of the vapors also reduced the temperature difference between the heat source and the organic fluid during the heat transfer process. The analysis was comparatively performed for several organic fluids such as R-245fa, R123, n-pentane and R717. The use of ammonia, that offered the possibility of superheating the vapors at the turbine inlet, brought a gain of mechanical power corresponding to 6% economy in the electrical energy input of the global plant.