The hydrogenation of triple and double carbon–carbon bonds in C4 molecules containing a single unsaturation has been investigated for the lowest index surfaces of the triad Ni, Pd, and Pt through first-principles simulations. Both low and high hydrogen coverage have been explored to identify the nature of the selectivity found in the experiments. The adsorption behavior of the alkynes and alkenes at high hydrogen concentrations differs from the structures in the infinite dilution-limit coverage which makes a significant contribution to selectivity. Structure sensitivity is also a consequence of the hydrogen coverage, at high contents (111) surfaces cannot trap the C4 molecules efficiently, and thus, the reactivity mainly occurs on the more open (100) surfaces. The combination of fast/slow elementary steps, crucial to eliminate trans-alkenes that are health threatening, is not possible for any of the metals studied, although some metals present slightly better behavior. Our study paves the way towards an integrative analysis of the hydrogenation process that accounts for high surface coverage, preferential adsorption, and kinetic contributions.