A theoretical study of the mechanism and kinetics of the OH radical reactions with aliphatic ethers is presented. Several methods were evaluated using the 6-311++G(d,p) basis set, with dimethyl ether as a test molecule. On the basis of the dimethyl ether results, the M05-2X functional was selected for the rest of the calculations. All the possible H abstraction paths have been modeled, and the importance of differentiating among H atoms bonded to the same C atom, according to their orientation with respect to the O atom in the ether, is analyzed. The rate coefficients are calculated using interpolated variational transition-state theory by mapping (IVTST-M), within the IVTST-M-4/4 scheme, in conjunction with small-curvature tunneling (SCT) corrections. The discussion is focused on the 280-400 K temperature range, but additional information is provided for an extended range (280-2000 K). Our analysis suggests a stepwise mechanism involving the formation of H bonded complexes in the entrance and exit channels. The vicinity of the O atom was found to increase the relative site reactivity. In fact, it was found to influence reactivity to a larger extent than the nature of the carbon site (primary, secondary, or tertiary). The overall agreement between the calculated and the available experimental data is very good and supports the reliability of the rate coefficients and the branching ratios proposed here for the first time. It also supports the performance of the M05-2X functional and the IVTST-M-4/4 scheme for kinetic calculations.