A simple reliability based framework is applied to calibrate a new set of fatigue design guidelines. This new guideline considers two different approaches for the assessment of both loads, stresses and local stress raising effects, and partial safety factors must be given for any combination of these approaches. For the calibration the lognormal reliability format is adopted because the hereby derived partial safety factors can be combined arbitrarily. This means that with a few basic partial safety factors, the combination of partial safety factors to be applied together with any combination of calculation approaches can be determined easily. In the present paper both the adopted reliability format, the applied modeling of uncertainties and the selected target safety index are explained. Based on this the new guideline is calibrated and the derived partial safety factors are presented. Finally, the new guideline is applied through a numerical example in order to show the applicability of the calibrated partial safety factors, and satisfactory results are found.