Rate coefficients for the reaction of the hydroxyl radical with CH3OCH2F (HFE‐161) were computed using transition state theory coupled with ab initio methods, viz., MP2, G3MP2, and G3B3 theories in the temperature range of 200–400 K. Structures of the reactants and transition states (TSs) were optimized at MP2(FULL) and B3LYP level of theories with 6‐31G* and 6‐311++G** basis sets. The potential energy surface was scanned at both the level of theories. Five different TSs were identified for each rotamer. Calculations of Intrinsic reaction coordinates were performed to confirm the existence of all the TSs. The kinetic parameters due to all different TSs are reported in this article. The rate coefficients for the title reaction were computed to be k = (9 ± 1.08) × 10−13 exp [−(1,713 ± 33)/T] cm3 molecule−1 s−1 at MP2, k = (7.36 ± 0.42) × 10−13 exp [−(198 ± 16)/T] cm3 molecule−1 s−1 at G3MP2 and k = (5.36 ± 1.57) × 10−13 exp [−(412 ± 81)/T] cm3 molecule−1 s−1 at G3B3 theories. The atmospheric lifetimes of CH3OCH2F at MP2, G3MP2, and G3B3 level of theories were estimated to be 20, 0.1, and 0.3 years, respectively.