An advanced theory of separation by the thermal diffusion method is proposed which accounts for isotope exchange reactions on the surface of the hot wire of the separation unit in a ternary isotopic mixture such as the D2-HD-H2 system or the T2-HT-H2 system. The theory has been developed in order to evaluate the performance of recovery of tritium and the separation rate from tritiated hydrogen gas by this process.The proposed theory can be applied not only to the batch process (total reflux process) but also to the continuous draw-off process for the simulation of mechanisms for D- or T-enrichment from a mixture of hydrogen isotopes. A theoretical model is derived on the basis of a ternary system, and the concept of ternary transport relations, a thermal diffusion coefficient correction factor and the effect of the isotope exchange reaction on the hot wall surface are introduced. Although the model is formally for a ternary system, the theory is also applicable even if the isotopic concentration of one or two components is extremely low.Overall separation performance decreases due to the isotope exchange reaction as compared with that with no reaction. It is very important to know that the existence of the T2 molecule and also of the isotope exchange reaction play significant roles in the separation performance of tritium, even at a tracer level of tritium.