Ru and Rh nanoparticles catalyze the selective H/D exchange in phosphines using D2 as the deuterium source. The position of the deuterium incorporation is determined by the structure of the P-based substrates, while activity depends on the nature of the metal, the properties of the stabilizing agents, and the type of the substituent on phosphorus. The appropriate catalyst can thus be selected either for the exclusive H/D exchange in aromatic rings or also for alkyl substituents. The selectivity observed in each case provides relevant information on the coordination mode of the ligand. Density functional theory calculations provide insights into the H/D exchange mechanism and reveal a strong influence of the phosphine structure on the selectivity. The isotope exchange proceeds via C-H bond activation at nanoparticle edges. Phosphines with strong coordination through the phosphorus atom such as PPh3 or PPh2Me show preferred deuteration at ortho positions of aromatic rings and at the methyl substituents. This selectivity is observed because the corresponding C-H moieties can interact with the nanoparticle surface while the phosphine is P-coordinated, and the C-H activation results in stable metallacyclic intermediates. For weakly coordinating phosphines such as P(o-tolyl)3, the interaction with the nanoparticle can occur directly through phosphine substituents, and then, other deuteration patterns are observed.