Deactivation by coke deposition is severe in the direct synthesis of dimethyl ether from (H-2 + CO) on a CuO-ZnO-Al2O3/gamma-Al2O3 catalyst. The results of coke temperature-programmed oxidation (TPO) and the effect of operating conditions (space time, temperature, pressure, and H-2/CO molar ratio in the feed) on coke deposition and evolution with time-on-stream of product distribution show that coke deactivates the metallic function. This coke is formed by degradation of intermediate oxygenates in methanol synthesis, which affects this reaction and favors the reactions of methanation and Fischer-Tropsch synthesis, which are not affected by deactivation. The fact that coke formation takes place in parallel with methanol synthesis advises using reaction conditions under which a balance is struck between both reactions: 275 degrees C, 20 bar, H-2/CO molar ratio = 2/1.