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Dimethyl ether (DME) represents a promising fuel for heavy-duty engines thanks to its high cetane number, volatility, absence of aromatics, reduced tank-to-wheel CO2 emissions compared to Diesel fuel and the possibility to be produced from renewable energy sources. However, optimization of compression-ignition engines fueled with DME requires suitable computational tools to design dedicated injection and combustion systems: reduced injection pressures and increased nozzle diameters are expected compared to conventional Diesel engines, which influences both the air-fuel mixing and the combustion process. This work intends to evaluate the validity of two different combustion models for the prediction of performance and pollutant emissions in compression-ignition engines operating with DME. The first one is the Representative Interactive Flamelet while the second is the Approximated Diffusive Flamelet.