An assessment of the effects of microstructure on fatigue crack initiation and short crack growth in a turbine disc nickel-base superalloy at 650∞C in air is presented. U720Li and microstructural variants of U720Li, i.e. U720Li-LG (large grain variant) and U720Li-LP (large intragranular coherent g' precipitate variant) have been assessed by uninterrupted and replicated short crack tests in polished U-notch specimens using a 1-1-1-1 trapezoidal loading cycle at nominal stress levels ranging between 700 and 850 MPa (calculated in the uncracked ligament). Crack initiation was primarily due to porosity on or near the surface but also due to grain boundary oxidation. Initial transgranular crack growth across 4-6 grains in air was noted at short crack lengths before oxidation-assisted intergranular crack growth modes were established at larger crack lengths. At a nominal applied stress of 840MPa, U720Li and U720Li-LP show similar fatigue lifetimes while U720Li-LG demonstrates a significantly improved fatigue lifetime, particularly when lifetimes are compared on a local strain range basis. A larger grain size gave the most significant performance benefits in terms of overall fatigue lifetime under these test conditions.