DFT-based reaction profiles and microkinetic simulations were used to describe the catalytic selective hydrogenation of acetylene on Ni, Ni3In, NiIn, and Ni2In3 model intermetallic surfaces. Among the NixIny intermetallic catalysts, NiIn showed the highest ethylene yield. Decreased formation of ethane was observed on NiIn and Ni2In3 accompanied by increased formation of oligomers compared to Ni and Ni3In. This emphasizes the significance of accounting for the oligomerization reactions when evaluating the selectivity of the catalysts. Inconsistent acetylene coverage was obtained when performing microkinetic simulations using free energy values calculated at low acetylene coverage, while a fully consistent coverage was obtained using high-coverage free energy values. Results from the high-coverage microkinetic model showed that the presence of In on the catalytic surface decreased the rate of acetylene consumption with a trade-off relation between activity and selectivity. Simulations in the absence of ethylene in the feed confirmed that ethylene hydrogenation and acetylene C–C coupling were the primary sources for ethane and oligomer formation, respectively. This study highlights the importance of considering oligomerization reactions, coverage effect, and feed composition when describing the activity and the selectivity of catalysts during the competitive hydrogenation of alkynes.