The analytical potential energy function of HDO is constructed at first using the many-body expansion method. The reaction dynamics of O+HD (v = 0, j = 0) in five product channels are all studied by quasi-classical trajec-tory (QCT) method. The results show that the long-lived complex compound HDO is the dominant product at low collision energy. With increasing collision energy, O+HD → OH+D and O+HD → OD+H exchange reactions will occur with remarkable characteristics, such as near threshold energies, different reaction probabilities, and different reaction cross sections, implying the isotopic effect between H and D. With further increasing collision energy (e.g., up to 502.08 kJ/mol), O+HD → O+H+D will occur and induce the complete dissociation into single O, H, and D atoms.