Abstract Recent astronomical observations of both isomers E and Z of imines such as cyanomethanimine, ethanimine, and 2-propyn-1-imine have revealed that the abundances in the interstellar medium (ISM) of these isomers differ by factors of ∼3–10. Several theories have been proposed to explain the observed behavior, but none of them successfully explains the [E]/[Z] ratios. In this work we present a detailed study of the kinetics of the one-step E-Z isomerization reactions of cyanomethanimine, ethanimine, and 2-propyn-1-imine under interstellar conditions (in the 10–400 K temperature range). This reaction was previously thought to be nonviable in the ISM due to its associated high-energy barrier (about 13,000 K). In this Letter, we show that considering the multidimensional small curvature tunneling approximation, the tunneling effect enables the isomerization even at low temperatures. This is due to the fact that the representative tunneling energy lies in the vibrational ground state of the least stable isomer up to approximately 150 K, making the reaction constants of the isomerization from the least stable to the most stable isomer basically constant. The predicted [E]/[Z] ratios are almost the same as those reported from the astronomical observations for all imines observed. This study demonstrates that the [E]/[Z] ratio of imines in the ISM strongly depends on their relative stability.