An interatomic potential for the Ni-Al system is presented within the third-generation charge optimized many-body (COMB3) formalism. The potential has been optimized for Ni3Al, or the γ' phase in Ni-based superalloys. The formation energies predicted for other Ni-Al phases are in reasonable agreement with first-principles results. The potential further predicts good mechanical properties for Ni3Al, which includes the values of the complex stacking fault (CSF) and the anti-phase boundary (APB) energies for the (1 1 1) and (1 0 0) planes. It is also used to investigate dislocation propagation across the Ni3Al (1 1 0)-Ni (1 1 0) interface, and the results are consistent with simulation results reported in the literature. The potential is further used in combination with a recent COMB3 potential for Al2O3 to investigate the Ni3Al (1 1 1)-Al2O3 (0 0 01) interface, which has not been modeled previously at the classical atomistic level due to the lack of a reactive potential to describe both Ni3Al and Al2O3 as well as interactions between them. The calculated work of adhesion for this interface is predicted to be 1.85 J m(-2), which is in agreement with available experimental data. The predicted interlayer distance is further consistent with the available first-principles results for Ni (1 1 1)-Al2O3 (0 0 0 1).