The paper focuses on experimental and numerical fatigue assessment procedures to evaluate the influence of multi-axial stress state caused by high centrifugal forces superimposed with bending loads due to blade vibrations on the lifetime of end stage blades from steam turbines. The experimental investigations on original-sized end stage blades were carried out on a test rig specially developed for high forces and multicomponent force application. This was based on detailed numerical simulations by the MPA University of Stuttgart. During the fractographic postexaminations of the tested blades using magnetic particle inspection, light and scanning electron microscopes, two competing damage mechanisms were identified that occurred at different locations. Numerical investigations by means of elastic–plastic finite element analyses were carried out to estimate the local stress conditions acting in the blade root. The local stresses and strains were postprocessed using the critical plane approach and advanced multi-axial fatigue damage parameters. Due to the high stress gradients at the edge of contact, over-conservative predictions may result if their effects are not taken into account. Based on the critical plane method in conjunction with fatigue damage parameters, an approach taking the stress gradient into consideration was developed to predict the fatigue life of the end stage blades. The approach is verified by the component tests on original-sized blades.