Fourier transform infrared spectroscopy has been used to follow the reaction of CH3OCF2CHF2 with either Cl or OH radicals within a photoreactor. Rate constants of k(OH + CH3OCF2CHF2) = (2.25 ± 0.60) × 10–14 cm3 molecule–1 s–1 and k(Cl + CH3OCF2CHF2) = (2.50 ± 0.39) × 10–13 cm3 molecule–1 s–1 were determined at 296 ± 2 K. Theoretical and experimental investigation of the Cl + CH3OCF2CHF2 reaction identified the formation of two main products, HC(O)OCF2CHF2 and COF2. Chlorine (and OH) radicals react with CH3OCF2CHF2 by H-abstraction from either the −CH3 or −CHF2 site. Abstraction from the −CH3 site was determined to constitute at least 60%, as determined from the formation of the primary product, HC(O)OCF2CHF2, which can only form from this abstraction site. At longer reaction times, HC(O)OCF2CHF2 further reacts and the yield of COF2 approaches two, the maximum possible with the number of F atoms in the reactant. The atmospheric lifetime of CH3OCF2CHF2 with OH radicals was determined to be 1.4 years. The global warming potentials over 20-, 100-, and 500-year time horizons were estimated to be 325, 88, and 25, respectively.