A detailed thermodynamic analysis of single-step synthesis of dimethyl ether (DME) from syngas has been performed. From experiments and theoretical calculations, a suitable thermodynamic model based on Reid's thermodynamic data and the Soave-Redlich-Kwong equation of state was determined. Using this model, a careful analysis of direct synthesis of dimethyl ether from syngas was carried out. Reaction synergy in the synthesis can greatly improve CO conversion and DME yield. Lower temperatures and higher pressures favor higher CO conversion and DME yield. Compared to methanol synthesis, however, the temperature has a smaller effect on the reaction. The direct synthesis of dimethyl ether can exploit CO-rich syngas efficiently due to the maximum DME yield obtained at H2/(CO+CO2) mole ratio =1. A small amount of CO2 in the reactant mixture has little effect on the reaction. Under conditions of H2/(CO+CO2) feedstock, water in the system can improve the reaction performance.