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Wastewater treatment stations take advantage of the biogas produced from sludge in anaerobic digesters to generate electricity (reciprocating gas engines) and heat (cooling water and engine exhaust gases). A fraction of this electricity is used to operate the plant while the remaining is sold to the grid. Heat is almost entirely used to support the endothermic anaerobic digestion and a minimum fraction of it is rejected to the environment at a set of fan coolers. This generic description is applicable to on-design conditions. Nevertheless, the operating conditions of the plant present a large seasonal variation so it is commonly found that the fraction of heat rejected to the atmosphere increases significantly at certain times of the year. Moreover, the heat available in the exhaust gases of the reciprocating engine is at a very high temperature (around 650 ºC), which is far from the temperature at which heat is needed for the digestion of sludge (around 40 ºC in the digesters). This temperature difference offers an opportunity to introduce an intermediate system between the engines and the digesters that makes use of a fraction of the available heat to convert it into electricity. An Organic Rankine Cycle (ORC) with an appropriate working fluid is an adequate candidate for these hot/cold temperature sources. In this paper, the techno-economic effect of adding an Organic Rankine Cycle as the intermediate system of an existing wastewater treatment station is analysed. On this purpose, different working fluids and system layouts have been studied for a reference wastewater treatment station giving rise to optimal systems configurations. The proposed systems yield very promising results with regard to global efficiency and electricity production (thermodynamically and economically).