Alloy 718 for forged parts can form a wide range of microstructures through a variety of thermo-mechanical processes, depending on the number of remelting processes, temperature and holding time of homogenization annealing, cogging and the number of forging steps depending on the forming characteristics. In industrial practice, these processing steps are tailored to achieve specific mechanical and microstructural properties in the final product. In the present work, we investigate the dependence of the threshold of stress intensity factor range ∆Kth on associated microstructural elements, namely grain size and distribution. For this purpose, a series of tests with different starting microstructures were performed at the falling stress intensity factor range, ∆K, and a load ratio of R = 0.1 to evaluate the different threshold values. Fracture initiation and crack propagation were analyzed afterward using scanning electron microscopy of the resulting fracture surfaces. In order to obtain comparable initial conditions, all specimens were brought to the same strength level by means of a two-stage aging heat treatment. In the future, this knowledge shall be used in the context of simulation-aided product development for estimating local fatigue crack propagation properties of simulated microstructures obtained from forging and heat treatment modeling.