This paper provides a sensitivity study on microstructure of aluminium alloy EN AC 46200 in terms of secondary dendrite arm spacing, porosity distribution and heat-treatment condition on fatigue failure mechanisms by constant amplitude loading at ambient temperature. The observed failure mechanisms are shrinkage porosity, slip bands and bi-films, which depend on the process and load settings. Summing up, the study improves the understanding of changing failure mechanisms in complex modern cast parts, inheriting varying cooling rates and heat treatment conditions.