In order to elucidate the role of solutes in vanadium alloys, the solute diffusions and the interactions of solute–solute and solute-vacancy have been investigated by means of the first-principles calculations. It is shown that large solutes are energetically favorable to combine with adjacent solute and to form the solute–solute nearest-neighbor pairs. In order to obtain qualitative understanding, the charge density differences for some special solute–solute binding are plotted to analyze the bonding interaction between solute atom and their nearest-neighbor host atoms. The solute–solute binding energies indicated that apart from the 3d transition metals, there is a clear trend of increasing binding energy with increasing solute volume. In particular, large solutes have larger binding energies for bonding with vacancies and can be considered as vacancy trappers in the crystal. As a comparison with solute diffusions, the self-diffusion coefficients of vanadium are determined. Activation energies for vacancy-mediated solute diffusion in vanadium are also determined. We conclude that the major contribution to the activation energy comes from the diffusion energy barrier, and both all follow the same trend. The noble metals have higher migration barriers than others, which means that these elements are inactive in the vanadium alloys. By contrast, the barriers for the large solutes almost cease to exist due to the formation of stable solute-centered divacancy.