Methanol dehydration to dimethyl ether (DME) has been carried out in a two-stage autothermal millisecond residence time reactor using a noble metal coated catalyst in the upstream stage to generate heat and zeolite in the downstream stage to dehydrate methanol with a total residence time of less than 100 ms. Two reactor configurations have been examined: (1) methanol fed from the top of the reactor with hydrogen as sacrificial fuel and (2) methanol fed between the two stages with methane as a sacrificial fuel. Methanol dehydration was also explored under isothermal conditions to compare with the results obtained under autothermal conditions. For autothermal experiments, reaction temperature and product distribution of the second stage was adjusted by varying the fuel to oxygen ratio and distance between two stages. The DME yield of the autothermal reactor with side-entering methanol was comparable to that of methanol dehydration reaction under isothermal conditions and was much better than the methanol top-feed configuration. The highest yield of DME obtained was similar to 80% at C/O ratio of 1.0 which was comparable to the non-autothermal values reported in literature (similar to 80%) and close to equilibrium yield (84%). This demonstrates the ability to synthesize DME in staged autothermal reactors with short contact time, high yield and no external heating. This also shows that noble metal catalysts can be integrated with zeolite catalysts for upgrading oxygenated compounds to more energetically dense compounds in compact reactors having multiple feeds. (C) 2011 Elsevier B.V. All rights reserved.