We describe studies of the thermal guanidine metathesis (TGM) reaction, a reversible transformation that results in exchange of N-substituents of the guanidine functional group. By comparing the effects of discrete structural variations, we find that steric congestion is an important factor in determining both the equilibrium guanidine composition and the reaction kinetics. The alkyl versus aryl nature of N-substitution also plays an essential role in the reaction rate, up to the point that minimal TGM reactivity is observed when the guanidine contains wholly alkyl substituents. Furthermore, we demonstrate that TGM occurs under thermodynamic control and present evidence that it proceeds by a dissociative mechanism, supported by direct observation of a carbodiimide intermediate.