This paper deals with different failure mechanisms in evaluated defect distributions and their impact on fatigue strength. Due to modern lightweight design of complex casting components, strongly varying local casting process conditions may occur, resulting in severe changes of mechanical properties. Two different aluminium alloys in peak hardness heat treatment condition, namely EN AC46200 and EN AC42100, were studied covering different local casting process conditions, e.g. variations in local cooling rate. Quasistatic investigations revealed quite strongly varying mechanical properties of the selected sample position for the two alloys, featuring a broad range of microstructural details. Consequently, varying fatigue strength levels are determined. Fractography yields diverse failure mechanisms regarding technical crack initiation. For the alloy EN AC 46200, mainly porosity induced failure is observed for all investigated samples covering both fine and coarse microstructure. Next, computed tomography (CT) investigations proved that the evaluated extreme value defect distribution matches well to fractographic results. Moreover, the alloy EN AC 42100 revealed some additional failure mechanisms besides porosity induced failure, for example oxide films, slip areas or inclusions, which cannot be properly detected by computed tomography. Thus, fatigue assessment methodologies of Tiryakioğlu and Murakami were used with some modifications to assess the fatigue strength of the investigated materials using evaluated defect distributions of varying failure mechanisms. The fatigue model of Tiryakioğlu reveals a slightly conservative fatigue design for all investigated defects for alloy EN AC 42100, but assess the fatigue life in case of EN AC 46200 quite well. The modified method of Murakami leads to quite conservative fatigue strength in case of alloy EN AC 46200, whereas the alloy EN AC 42100 exhibits a basic matching within a scatter index of ten percent in strength. Summarizing, the method by Tiryakioğlu can be well applied for imperfections which can be identified by CT, such as pores and inclusions. Murakami´s approach is applicable for different imperfection types yielding a slightly increased scatter index for fatigue design of aluminium castings.