The numerical simulation of crack closure is employed to assist on the prediction of crack growth rate. Under fatigue load, the stress-strain response of metals is altered due to cyclic loading. For this reason, the material properties characterization is of prime concern as an input parameter to obtain reliable results. From numerical simulations, it was observed that simple material models do not provide accurate data for long crack lengths. In this paper, the effect that different hardening models have on the opening response of a cracked component when it is subject to variable amplitude loading is analyzed. The interaction effects (crack arrest/acceleration) for long crack length simulation are specially highlighted. For this purpose, a 6082-T6 aluminium alloy was analyzed experimentally and numerically in order to measure crack closure, and then, those data were used to predict fatigue crack growth rate under different patterns of overload. The Paris equation and the Elber crack closure concept were employed. The results showed that small variations in the opening stresses obtained from different material models produce high overestimated simulations of crack growth rate. Also, it was proved that the crack closure mechanism is able to take into account interaction effects due to variable amplitude loading.