Cooling of thermal power stations requires large amounts of surface water and contributes to the increasing pressure on water resources. Water use efficiency of recirculating cooling towers (CT) is often kept low to prevent scaling. Partial desalination of CT feed water with membrane capacitive deionization (MDCI) can improve water quality but also results in additional water loss. A response surface methodology is presented in which optimal process conditions of the MCDI-CT system are determined in view of water use efficiency and cost. Maximal water use efficiency at minimal cost is found for high adsorption current (2.5 A) and short adsorption time (900 s). Estimated cost for MCDI to realize maximal MCDI-CT water use efficiency is relatively high (2.0–3.1 € m−3evap), which limits applicability to plants facing high intake water costs or water uptake limitations. MCDI-CT pilot tests show that water use efficiency strongly depends on CT operational pH. To allow comparison among pilot test runs, simulation software is used to recalculate CaCO3 scaling and acid dosage for equal operational pH. Comparison at equal pH shows that MCDI technology allows a clear reduction of CT water consumption (74%–80%) and acid dosage (63%–80%) at pH 8.5.