Al-Si-Mg alloys are widely used in the automotive industry for the production of engine components. Due to the new stringent emissions standards, these components undergo highertemperatures than in the past; as a result, alloys with higher thermal stability, such as the Al-Si-Cu-Mg, are currently under investigation.The present paper aims at widening the knowledge on the relationship between room temperature (RT) and high temperature fatigue behaviour of A354 and C355 alloys and their microstructural features, in particular, secondary dendrite arm spacing (SDAS) and intermetallic compounds. Samples for fatigue characterization were hot isostatic pressed, aiming to avoid the effect of solidification defects.The results of microstructural analyses and rotating bending fatigue tests highlighted that (i) SDAS influences room temperature fatigue behaviour of the peak-aged A354 and C355 alloys, while its effect on the overaged alloys at high temperature is negligible; (ii) fatigue cracks nucleated mostly from large intermetallic compounds; (iii) at room temperature, C355 alloy is characterized by higher fatigue strength (151 and 135. MPa for fine and coarse SDAS, respectively) in comparison to A354 alloy (133 and 113. MPa); after overaging and testing at high temperature, the behaviour of the two alloys is comparable. A good correlation between ultimate tensile strength and fatigue resistance was found, independent of microstructure and aging condition.