Molecular dynamics (MD) simulations using a recently developed first-principles-based embedded-atom-method (EAM) potential are used to simulate the exothermic alloying reactions of a Ni/Al bilayer initially equilibrated at 1200 K. Simulations are performed in the isobaric–isoenthalpic (NPH) ensemble, which provides insight into the influence of pressure on atomic mixing and the subsequent alloying reaction. For pressures lower than 8 GPa, the mechanism of mixing is the same: as mixing and reaction occur at the interface, the heat generated first melts the Al layer, and subsequent mixing leads to further heat generation after which the Ni layer melts, leading to additional mixing until the alloying reactions are completed. However, for simulations at pressures higher than 8 GPa, the reaction does not occur within the time interval of the simulation. The results will be compared with our previous simulations of a Ni/Al bilayer using a different interatomic potential, which predicts substantially different pressure-dependent melting behavior of the pure components. This comparative study suggests that pressure-dependent melting behavior of components of reactive materials can be used to influence reaction rates and mechanisms.