Reactions are known where the deuterated species reacts faster than the undeuterated analogue, and these cases are said to exhibit inverse kinetic isotope effects (IKIE). IKIE's are often observed in the reductive elimination of alkyl metal hydrides, e.g. (MeNCHCHNMe)PtMe(H). In such cases the C-D bond in the transition state, an agostic species, is highly stabilized relative to the C–H bond.
An inverse effect can also occur in a multistep reaction if the overall rate constant depends on a pre-equilibria prior to the rate-determining step which has an inverse equilibrium isotope effect. For example, the rates of acid-catalyzed reactions are usually 2-3 times greater for reactions in DO catalyzed by DO than for the analogous reactions in HO catalyzed by HO This can be explained for a mechanism of specific hydrogen-ion catalysis of a reactant R by HO (or DO).
:HO + R  RH + HO
:RH + HO → HO + P
The rate of formation of products is then d[P]/dt = k[RH] = kK[HO][R] = k[HO][R]. In the first step, HO is usually a stronger acid than RH. Deuteration shifts the equilibrium toward the more strongly bound acid species RD in which the effect of deuteration on zero-point vibrational energy is greater, so that the deuterated equilibrium constant K is greater than K. This equilibrium isotope effect in the first step usually outweighs the kinetic isotope effect in the second step, so that there is an apparent inverse isotope effect and the observed overall rate constant k = kK decreases.