This study investigates the effect of hot isostatic pressing (HIPping) on the static and fatigue properties of sand-casting A356 aluminium alloys. HIPping is a method to improve the fatigue properties in aluminium cast material by reducing or eliminating the inner porosities. Investigation of the complex interaction between the microstructural features on mechanical properties before and after the HIPping process was examined using computed tomography and scanning electron microscopy (SEM). Castings generally contain pores and defects that have a detrimental impact on the fatigue properties. The HIPping process closes the porosities in all investigated samples with an increase in density. Without significant defects, the mechanical performance improved in the finer microstructure. However, a considerable variation in the results was found between the different conditions, whereas the coarser microstructure with larger porosities before HIPping showed remarkably reduced results. The high-cycle fatigue-tested samples showed reduced fatigue propagation zone in the coarser microstructure. Moreover, large cleavage areas containing bifilms in the fracture surfaces indicate that the healing process of porosities is inefficient. These porosities are closed but not healed, resulting in a detrimental effect on the static and dynamic properties.