Due to the increase in energy prices and spiralling consumption, there is a need to greatly reduce the cost of electricity within data centers, where it makes up 50% of the total cost of the IT infrastructure. A technological solution to this is using on-chip cooling with a single-phase or evaporating liquid to replace energy intensive air-cooling. The energy carried away by the liquid or vapour can also potentially be used in district heating, as an example. Thus, the important issue here is “what is the most energy efficient heat removal process?” As an answer, this paper presents a direct comparison of single-phase water, a 50% water ethylene glycol mixture and several two-phase refrigerants, including the new fourth generation refrigerants HFO1234yf and HFO1234ze. Two-phase cooling using HFC134a had an average junction temperature 9 to 15˚C lower than for single-phase cooling, while the required pumping power for the CPU cooling element for single-phase cooling was on the order of 20-130 times higher to achieve the same junction temperature uniformity. Hot-spot simulations also showed that two-phase refrigerant cooling was able to adjust to local hot-spots because of flow boiling's dependency on the local heat flux, with junction temperatures being 20 to 30˚C lower when compared to water and the 50% water-ethylene glycol mixture, respectively. An exergy analysis was developed considering a cooling cycle composed by a pump, a condenser and a multi-microchannel cooler. The focus was to show the exergetic efficiency of each component and of the entire cycle when the subject energy recovery is considered. Water and HFC134a were the working fluids evaluated in such analysis. The overall exergetic efficiency was higher when using HFC134a (about 2%) and the exergy destroyed, i.e. irreversibilities, showed that the cooling cycle proposed still have a huge potential to increase the thermodynamic performance.