AbstractThe ring‐opening reaction of the cyclopropylcarbinyl radical proceeds via heavy‐atom tunneling at low temperature. We used instanton theory to calculate tunneling rates and kinetic isotope effects with on‐the‐fly calculation of energies by density functional theory (B3LYP). The accuracy was verified by explicitly correlated coupled‐cluster calculations (UCCSD(T)‐F12). At cryogenic temperatures, we found protium/deuterium KIEs up to 13 and inverse KIEs down to 0.2. We also studied an intramolecular tautomerization reaction. A simple and computationally efficient method is proposed to calculate KIEs with the instanton method: the instanton path is assumed to be independent of the atomic masses. This results in surprisingly good estimates of the KIEs for the cyclopropylcarbinyl radical and for the secondary KIEs of the tautomerization. Challenges and capabilities of the instanton method for calculating KIEs are discussed. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011